Knockdown of ACC1 promotes migration of esophageal cancer cell / 中华肿瘤杂志

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 μmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.

Are Saunas Beneficial or Harmful for Autosomal Dominant Polycystic Kidney Disease? Examination with Model Mouse / 日本温泉気候物理医学会雑誌

  Background: Heat shock proteins (Hsps), expression of which are induced by thermal treatment, function in the protection of kidneys by suppressing apoptosis and maintaining renal tubular viability. Moreover, recently, it has been indicated that the expression of Hsps can be a therapeutic target for autosomal dominant polycystic kidney disease (ADPKD). We investigated the effect of dry sauna therapy on ADPKD model mice.  Methods and Results: The mice (male DBA/2FG-pcy mice) were categorized into three groups: controls, TS: pcy mice subjected to prolonged sauna with administered water containing 4% sucrose, SW: pcy mice administered water containing 4% sucrose. The TS group was subjected to sauna sessions twice a week for four weeks. The TS group attained and were maintained at rectal temperatures of approximately 39.0°C, until they were carefully removed from the far infrared-ray device. After 4 weeks of sauna treatment, creatinine and blood-urea-nitrogen (BUN) levels determined by an enzymatic method. The heat shock protein (HSP) or cell growth and size related proteins were analyzed by western blotting. The TS group exhibited marginally higher creatinine and BUN levels than did the control and SW groups, however, the differences were not significant. However, cyst enlargement in the TS group reduced significantly compared to that of the control group. HSP90 expression was slightly decreased in the TS and SW groups relative to the control group (p < 0.01 or p < 0.001, vs. control), as was Erk expression, which is linked to cyst development and proliferation (p < 0.05, TS vs. control). Hsp27 expression and phosphorylation level in the SW group were comparable with that of the control group. However, the TS group had increased levels of Hsp27 and phosphorylation (NS). The expression of pro-caspase-3 in the TS group was marginally lower than that in the control group. However, the activity of caspase-3 in all groups showed no differences.  Conclusion: The findings of this study indicated that 4 weeks of sauna treatment could cause transient dehydration and related renal dysfunction and led to the risk of stimulating cyst growth by increased Hsp27 expression. Moreover, we concluded that prevention of dehydration and cyst growth could be suppressed by taking an appropriate amount of water directly after sauna treatment.

Are Saunas Beneficial or Harmful for Autosomal Dominant Polycystic Kidney Disease? Examination with Model Mouse / 日本温泉気候物理医学会雑誌

  Background: Heat shock proteins (Hsps), expression of which are induced by thermal treatment, function in the protection of kidneys by suppressing apoptosis and maintaining renal tubular viability. Moreover, recently, it has been indicated that the expression of Hsps can be a therapeutic target for autosomal dominant polycystic kidney disease (ADPKD). We investigated the effect of dry sauna therapy on ADPKD model mice.  Methods and Results: The mice (male DBA/2FG-pcy mice) were categorized into three groups: controls, TS: pcy mice subjected to prolonged sauna with administered water containing 4% sucrose, SW: pcy mice administered water containing 4% sucrose. The TS group was subjected to sauna sessions twice a week for four weeks. The TS group attained and were maintained at rectal temperatures of approximately 39.0°C, until they were carefully removed from the far infrared-ray device. After 4 weeks of sauna treatment, creatinine and blood-urea-nitrogen (BUN) levels determined by an enzymatic method. The heat shock protein (HSP) or cell growth and size related proteins were analyzed by western blotting. The TS group exhibited marginally higher creatinine and BUN levels than did the control and SW groups, however, the differences were not significant. However, cyst enlargement in the TS group reduced significantly compared to that of the control group. HSP90 expression was slightly decreased in the TS and SW groups relative to the control group (p < 0.01 or p < 0.001, vs. control), as was Erk expression, which is linked to cyst development and proliferation (p < 0.05, TS vs. control). Hsp27 expression and phosphorylation level in the SW group were comparable with that of the control group. However, the TS group had increased levels of Hsp27 and phosphorylation (NS). The expression of pro-caspase-3 in the TS group was marginally lower than that in the control group. However, the activity of caspase-3 in all groups showed no differences.  Conclusion: The findings of this study indicated that 4 weeks of sauna treatment could cause transient dehydration and related renal dysfunction and led to the risk of stimulating cyst growth by increased Hsp27 expression. Moreover, we concluded that prevention of dehydration and cyst growth could be suppressed by taking an appropriate amount of water directly after sauna treatment.

Research progress on the role of heat shock protein 27 in prostate cancer / 中国药科大学学报

@#Prostate cancer is one of the most common cancers in adult men. Heat shock proteins (HSPs),as molecular chaperones widely involved in the pathogenesis,diagnosis,treatment and prognosis of various cancers,play crucial biological functions in prostate cancer and it can be considered as valuable biomarkers for cancer therapy, such as prostate-specific membrane antigen. As a member of the heat shock protein family, HSP27 is related to prostate cancer castration resistance,and its expression can promote tumor resistance,invasion and bone metastasis,making prostate cancer more invulnerable to treatments. Therefore,targeting HSP27 in prostate cancer can be perceived as one promising cancer treatment strategy. This article reviews the structure and function of HSP27,and its potential role on castration resistance and targeted therapy in order to provide a new theoretical basis for the clinical treatment of prostate cancer.

Research progress of heat shock protein 27 in thyroid cancer / 中国医师杂志

Heat shock protein 27 (HSP27) is an important member of the heat shock protein family.In addition to its well-known chaperone function,recent studies have shown that it has been expressed in some malignant tumors.A large number of studies have shown that there is a significant correlation between HSP27 and thyroid carcinoma.This article reviews the research progress of HSP27 in thyroid carcinoma.

Research progress of heat shock protein 27 in thyroid cancer / 中国医师杂志

Heat shock protein 27 (HSP27) is an important member of the heat shock protein family. In addition to its well-known chaperone function, recent studies have shown that it has been expressed in some malignant tumors. A large number of studies have shown that there is a significant correlation between HSP27 and thyroid carcinoma. This article reviews the research progress of HSP27 in thyroid carcinoma.

Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein / 中国结合医学杂志

OBJECTIVE@#To investigate the potential mechanisms that curcumin reverses 5-fluorouracil (5-FU) multidrug resistance (MDR).@*METHODS@#Cell growth and the inhibitory rate of curcumin (2-25 μg/mL) and/or 5-FU (0.05-1000 μg/mL) on human colon cancer HCT-8 and HCT-8/5-FU (5-FU-resistant cell line) were determined using cell counting kit-8 (CCK-8) assay. Apoptosis and cell cycle after 5-FU and/or curcumin treatment were detected by flow cytometry (FCM) and transmission electron microscopy (TEM). The expression of the multidrug resistance related factors p-glycoprotein (P-gp) and heat shock protein 27 (HSP-27) genes and proteins were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (WB), respectively.@*RESULTS@#The inhibitory rate of curcumin or 5-FU on HCT-8 and HCT-8/5-FU cells proliferation at exponential phase were in a dosedependent manner, HCT-8 cell line was more sensitive to curcumin or 5-FU when compared the inhibitory rate of HCT-8/5-FU. The 50% inhibitory concentration (IC) of combination 5-FU and curcumin (4.0 μg/mL) in HCT-8/5-FU was calculated as 179.26 μg/mL, with reversal fold of 1.85. Another IC of combination 5-FU and curcumin (5.5 μg/mL) in HCT-8/5-FU was calculated as 89.25 μg/mL, with reversal fold of 3.71. Synergistic effect of 5-FU and curcumin on HCT-8 and HCT-8/5-FU cells were found. The cell cycle analysis performed by FCM showed that HCT-8 and HCT-8/5-FU cells mostly accumulated at G/G phase, which suggested a synergistic effect of curcumin and 5-FU to induce apoptosis. FCM analysis found that the percentage of apoptosis of cells treated with curcumin, 5-FU and their combination were significantly increased compared to the control group (P<0.05), and the percentage of apoptosis of the combination groups were slightly higher than other groups (P<0.05). The mRNA levels of P-gp (0.28±0.02) and HSP-27 (0.28±0.09) in HCT-8/5-FU cells treated with combination drugs were lower than cells treated with 5-FU alone (P-gp, 0.48±0.07, P=0.009; HSP-27, 0.57±0.10, P=0.007). The protein levels of P-gp (0.25±0.06) and HSP-27 (0.09±0.02) in HCT-8/5-FU cells treated with combination drugs were decreased when compared to 5-FU alone (P-gp, 0.46±0.02, P=0.005; HSP-27, 0.43±0.01, P=0.000).@*CONCLUSIONS@#Curcumin can inhibit the proliferation of human colon cancer cells. Curcumin has the ability of reversal effects on the multidrug resistance of human colon cancer cells lines HCT-8/5-FU. Down-regulation of P-gp and HSP-27 may be the mechanism of curcumin reversing the drug resistance of HCT-8/5-FU to 5-FU.

Heat shock protein 27 mediates bortezomib-resistance of multiple myeloma cells / 肿瘤

Objective: To investigate the expression of heat shock protein 27 (HSP27) in multiple myeloma (MM) cells, and to explore its relationship with bortezomib (BTZ) resistance. Methods: The expression levels of HSP27 mRNA and protein in myeloma cells (CD38+/CD138+ plasma cells) of 22 patients with MM (12 newly treated patients and 10 relapsed patients after BTZ treatment) were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The BTZresistant U266/BTZ cell line was established, and CCK-8 assay was used to detect the effects of different concentrations of BTZ, doxorubicin and etoposide on the proliferation of U266/BTZ cells and the parent U266 cells. The expression levels of HSP27 mRNA and protein in U266/BTZ cells and U266 cells were also examined by real-time fluorescent quantitative PCR and Western blotting, respectively. The specific small interfering RNA (siRNA) was used to silence HSP 27 gene expression in U266/BTZ cells, and the impact of silencing HSP 27 gene expression on BTZ-induced apoptosis of U266/BTZ cells was assessed by FCM. Additionally, the U266 cells were treated with BTZ alone or in combination with p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor SB203580, then the expression levels of HSP27, phospho-HSP27 (p-HSP27), p38 MAPK, and p-p38 MAPK were measured by Western blotting. Finally, the recombinant lentivirus pCDH-CMV-MCS-EF1-copGFP-T2A-Puro/ HSP27 was constructed and infected into U266 cells to induce the overexpression of HSP 27 gene, then the activity of 20S proteasome in U266 cells with HSP 27 gene overexpression after treatment with different concentrations of BTZ was determined by fluorescence substrate method. Results: The expression levels of HSP27 mRNA and protein in myeloma cells from MM-relapsed patients were significantly higher than those in newly treated patients (both P < 0.01). BTZ-resistant myeloma cell line was successfully established, the half-maximal inhibitory concentration (IC50) of BTZ, doxorubicin and etoposide in BTZ-resistant U266/BTZ cells was significantly increased as compared with its parent U266 cells (all P < 0.01). The expressions of HSP27 mRNA and protein in U266/BTZ cells were significantly up-regulated (both P < 0.01). Silencing HSP 27 gene expression significantly increased BTZ-induced apoptotic rate of U266/BTZ cells (P < 0.01). Treatment with BTZ alone considerably up-regulated the expressions of HSP27, p-HSP27 and p-p38 MAPK in U266 cells, while this effect could be dramatically counteracted by pre-treatment with SB203580 (all P < 0.01). Furthermore, the overexpression of HSP 27 gene significantly reduced the inhibitory effects of BTZ at different concentrations on the activity of 20S proteasome in U266 cells (P < 0.01). Conclusion: The expression of HSP27 is closely related to BTZ-resistance of MM cells, which may be related to the BTZ exposure activating the p38 MAPK signaling pathway and up-regulating HSP27 expression, consequently decreasing the inhibitory effect of BTZ on proteasome activity through a feedback mechanism.

Combined Extracts of Artemisia and Green Tea, Mitigated Alcoholic Gastritis Via Enhanced Heat-shock Protein 27 / 대한소화기학회지

BACKGROUND/AIMS: Several lines of evidence from epidemiologic and laboratory studies have shown that the consumption of Artemisia or green tea extracts (MPGT) is inversely associated with the risk of alcohol-induced damage and other chronic diseases. Supported by previous studies showing that the combined extract of Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti-inflammatory actions against Helicobacter pylori-associated gastric diseases, it was hypothesized that MPGT can offer protection against alcoholic gastritis. METHODS: Ethanol was administered to induce gastric damage in Wistar rats, which had been pretreated with various doses of MPGT, to measure the rescuing action of a MPGT pretreatment against ethanol-induced gastric damage. In addition, the molecular mechanisms for the preventive effects were examined. RESULTS: The MPGT pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric damage, which was evidenced by the significant decrease in calcium-dependent phospholipase A2, MAPKs, and NF-κB levels compared to ethanol alone. Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase, whereas cyclooxygenase-2 was decreased significantly. All of these biochemical changes led to the significant alleviation of alcohol-associated gastric mucosal damage. Ethanol significantly increased the TUNEL positivity in the stomach, but MPGT decreased the apoptotic index significantly, which was associated with significantly lower pathological scores of ethanol-induced mucosal ulcerations. The significant protective changes observed alcoholic gastritis with MPGT were related to the increased expression of cytoprotective genes, such as heat-shock protein (HSP)27, HSP60, and PDGF. CONCLUSIONS: The efficient anti-inflammatory, anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient phytoceutical to rescue the stomach from alcoholic gastritis.

Lipopolysaccharide protects kidney ischemia-reperfusion injury by up-regulating heat shock protein-27 in mice / 第二军医大学学报

Objective To explore the effect of heat shock protein-27 (HSP27) in lipopolysaccharide (LPS)-induced renoprotection against ischemia-reperfusion (IR) injury in mice. Methods Male C57BL/6 mice were used for establishing renal IR injury model and the animals were divided into 4 groups: sham group, LPS+sham group, IR group, and LPS+IR group; each group was further divided into quercetin (200 mg/kg) subgroup and vehicle control subgroup. Renal IR model was established by right nephrectomy + clamping the left renal pedicle for 25 min. Mice were intraperitoneally injected with LPS (3 mg/kg body weight) 3 days prior to renal IR, and the expression of HSP27 was inhibited by quercetin (200 mg/kg), an inhibitor of HSP27 synthesis. 24 h after reperfusion, the extent of IR injury was evaluated by serum creatinine (Cr) and blood urea nitrogen (BUN) levels in abdominal aorta, and the degree of inflammatory reaction, expression of HSP27 protein and activity of apoptosis protein caspase-3 were evaluated in the left kidney. Results LPS pretreatment significantly reduced the levels of Cr and BUN in the serum, improved the expression level of HSP27, and reduced the degree of renal IR injury after renal IR (P<0.05). It was found that quercetin significantly inhibited the expression of HSP27 in the kidney (P<0.05). Quercetin could significantly weaken the alleviating effect of LPS on renal IR by elevating Cr and BUN levels and causing more severe inflammation reaction (P<0.05). In addition, LPS significantly reduced the activity of caspase-3 after renal IR, which could be significantly weakened by quercetin. Conclusion LPS pretreatment can relieve the renal IR injury in mice by up-regulating the expression of HSP27.

Effects of chemokine CCL2 on the p38MAPK-HSP27 pathway in the platelets / 解放军医学杂志

Objective To investigate whether chemokine CC motif 2 (CCL2) is involved in the high residual platelet response,and the mechanism of CCL2 being involved in the regulation of platelets.Methods Forty patients with ST elevation myocardial infarction (STEMI) were admitted.P2Y12 reaction unit (PRU) was detected by VerifyNow.Forty patients were divided into high platelet reactivity group (high reactivity group,n=24) and normal platelet reactivity group (normal reactivity group,n=16) according to the results of PRU detection.Plasma CCL2 concentration of the STEMI patients was examined by ELISA.The expressions of CCL2 and CCR2 in the platelets were detected by Western blotting.After CCL2 stimulation,the kinases of which phosphorylation was changed in the platelets were screened by ARY003B protein chips.The phosphorylation of p38MAPK and HSP27 in the platelets was tested by Western blotting after CCL2 stimulation in the presence or absence of CCR2 antagonist (RS 102895) or p38MAPK signal pathway inhibitor (SB 203580).Results The plasma CCL2 concentration of high reactivity group was markedly higher than that of normal reactivity group.Moreover,compared with normal reactivity group,the expressions of CCL2 and CCR2 in the platelets of high reactivity group significantly increased.After the platelets were stimulated by CCL2,the phosphorylation of p38α and HSP27 enhanced in the platelets by protein chips screening.When RS 102895 or SB 203580 was treated before CCL2 stimulation,the phosphorylation of p38MAPK and HSP27 decreased.Conclusions CCL2 participates in high residual platelet response in an autocrine/paracrine way.CCL2/CCR2 might affect the function ofplatelets through p38MAPKHSP27 signal pathway.

Effect of Qingyi Lidan Granule on Serum Levels of HMGB1, HSP70, HSP27 and IL-8 of Patients with Severe Acute Pancreatitis / 现代生物医学进展

Objective:To study the effect of Qingyi Lidan Granule on the serum levels of high mobility group box 1 (HMGB 1),heat shock protein 70 (HSP70),heat shock protein 27 (HSP27) and interleukin-8 (IL-8) of patients with severe acute pancreatitis.Methods:From August 2015 to July 2016,84 patients with severe acute pancreatitis in our hospital were selected and randomly divided into the observation group and the control group according to random number,42 cases in each group.The control group was given routine treatment,and the observation group was treated by Qingyi Lidan Granule on the basis of control group.The recovery of blood amylase to normal time,white blood cell recovery to normal time,recovery of gastrointestinal function to normal time and relieving time of abdominal pain,serum levels of HMGB1,HSP70,HSP72 and IL-8 in both groups were observed and compared before and after treatment.Results:After treatment,the total clinical effective rate of observation group was significantly higher than that of the control group[92.86％ (39/42) vs 71.43％ (30/42)] (P＜0.05).The recovery of blood amylase to normal time,white blood cell recovery to normal time,recovery of gastrointestinal function to normal time and relieving time of abdominal pain in the observation group were significantly shorter than those of the control group (P ＜0.05).Before treatment,no significant difference was found in the serum levels of HMGB 1,HSP70,HSP72,IL-8 between groups (P＞0.05).After treatment,the serum levels ofHMGB1,HSP70,HSP72 and IL-8 in both groups were significantly lower than those before treatment (P＜0.05).The levels ofHMGB1,HSP70,HSP72 and IL-8 in the observation group were lower than those in the control group (P＜0.05).Conclusion:Qingyi Lidan Granule could effectively reduce the levels of serum HMGB 1,H SP70,HSP27 and IL-8 and enhance the clinical curative effect of patients with severe acute pancreatitis.

Serum levels of phosphorylated heat shock protein 27 (pHSP27) are associated with bone mineral density in pre- & postmenopausal women: A pilot study.

Background & objectives: Phosphorylated heat shock protein 27 (pHSP27) has been implicated in the pathogenesis of osteoporosis. Oxidative stress and proinflammatory cytokines, which are known to be involved in aetiology of osteoporosis, can trigger HSP27 phosphorylation. Since pHSP27 is present in circulation, it was hypothesized that serum pHSP27 would be elevated in low bone mineral density (BMD) condition and might serve as an indicator of osteoporosis/osteopenia. Hence, the aim of this study was to examine serum levels of pHSP27 in relation with BMD in pre- and postmenopausal women. Methods: Premenopausal (30 to 40 yr) and postmenopausal (50 to 60 yr) women having either low BMD (osteopenia/osteoporosis) or high BMD were selected (n=80) from a prospective cohort (n=200). Serum levels of pHSP27; along with levels of oestradiol, malondialdehyde, total antioxidant capacity, interleukin (IL)-1, IL-6, tumour necrosis factor - alpha, (TNF-α), c-telopeptide fragments of collagen type I (CTX-1) and osteocalcin were estimated. Results: The serum levels of pHSP27 were significantly elevated in low BMD groups in premenopausal and postmenopausal categories (P<0.05). It also exhibited a significant odds ratio (OR) to differentiate between low and high BMD in both premenopausal (OR=1.734, P=0.013) and postmenopausal (OR=1.463, P=0.042) categories. Additionally, area under the curve to predict low BMD was non-significantly higher for pHSP27 than CTX-1 in premenopausal and postmenopausal categories. Interpretation & conclusions: This study highlights a novel relation between serum pHSP27 and BMD in Indian women however, these findings need to be confirmed in larger studies.

Growth Difference between CNE-2 and S-18 Cell Lines after Subcutaneous Xenograft / 昆明医科大学学报

Objective To study the growth difference and possible mechanism between nasopharyngeal carcinoma (NPC) cell line CNE-2 and its subclone S-18.Methods CNE-2 and S-18 cells were cultured in vitro.6 x 105 cells/mouse were xenografted subcutaneously in the back of nude mice.The volumes of rumors were measured on the 3 rd,7 th,10 th,14 th day after grafting.Mice were sacrificed on the 14 th day and tumors were isolated and weighed.RNA from tumor tissues were extracted and transcriptional levels of HSP27 and NF-K B were detected.Results (1) S-18,instead of CNE-2,grew to form tumor mass 7 days after xenografting subcutaneously;both cell lines formed tumor mass 10 days after xenografting,however,the volumes of S-18 tumors [(223.13 ± 21.32) mm3,10 th day;(420.25 ± 24.52) mm3,14 th day] were significant bigger than CNE-2tumors [(113.70±11.70) mm3,10thday;(279.86±25.78) mm3,14thday];The weights of S-18 umors were significantly higher than CNE-2 tumors on the 14 th day after xenografting;(2) The transcriptional levels of HSP27 and NF-KB in S-18 tumor were significantly higher than in CNE-2 tumor.Conclusion Xenografted S-18 NPC grows faster than Xenografted CNE-2 NPC.HSP27 and NF-κ B are probably involved in the regulation of growth in NPC.

Research progress of estrogen-mediated HSP27 in atherosclerosis / 中国药理学通报

Heat shock protein 27 ( HSP27 ) is an endogenous protein that plays an important role in a great variety of physio-logical and pathological processes. It can express a large number under body stress conditions. Recent studies have shown estro-gen upregulates the expression of HSP27 through a number of ways, playing a perfect “triple protection” role. In the early stage of atherosclerosis, estrogen induces the phosphorylation of HSP27 via PI3K/Akt signaling pathway. Phosphorylation of HSP27 can resist the injury of vascular endothelial cells( VECs) through an antioxidant and anti-apoptotic pathway as well as the inhibition of cytochrome C. In the stage of forming foam cells, estrogen induces the expression and release of HSP27 from mac-rophages by stimulating the estrogen receptor β ( ERβ) , then HSP27 inhibits the LDL uptake and the release of proinflammato-ry cytokine by binding scavenger receptor A ( SR-A) . During the proliferation and migration of vascular smooth muscle cells ( VSMCs) , estrogen induces estrogen receptor α ( ERα) and protein phosphatase 2 ( PP2A) to form a complex that enhances the activity of PP2A, then it can lead to the dephosphorylation of HSP27 and finally inhibit cells proliferation and migration. In summary, the anti-atherosclerotic effect of estrogen is closely re-lated to the role of HSP27. Given the side effects of estrogen re-placement therapy( MHT) , regulating HSP27 may provide a no-vel therapy for the prevention and treatment of cardiovascular dis-eases in menopausal women clinically.

Expression of heat shock protein 27, 60 and 90 in gastric cancer and its clinical value / 中国免疫学杂志

Objective: To investigate the expression of HSP-27,-60 and -90 in gastric cancer and its clinical significance. Methods:66 cases of gastric carcinoma was detected by immunohistochemistry HSP-27,60 and 90 of the expression and clinical significance of combined with clinical and pathological characteristics, tumor cell proliferation and survival analysis of three kinds of heat shock protein expression. Results: HSP-27,-60 and -90 were highly expressed in gastric cancer tissues. HSP-27 expression and tumor size (pT,P=0. 026),organ metastasis (pM,P=0. 046) and pathological staging (P=0. 041),HSP-27 staining intensity and lymph node status were significantly correlated ( pN, P=0. 042 ) . HSP-60 expression was associated with gender ( P=0. 011),and HSP-60 staining intensity was associated with age (P=0. 027) and tumor grade (P=0. 031). There was no correlation between HSP-90 expression and the clinical pathological parameters of this study; however, the intensity of HSP-90 staining was significantly correlated with tumor size (P=0. 020,pT). Single factor analysis showed that HSP-90 was significantly associated with longer survival (P=0. 033). Multivariate analysis demonstrated that HSP-90 was highly expressed as an independent prognostic factor for gastric cancer (P=0. 026). Conclusion: the HSP-27,-60 and -90 and some clinical pathological parameters. These parameters is very important for the treatment of patients with gastric cancer. The high expression of HSP-90 in patients with gastric cancer were inde-pendent prognostic indicators.

The Prognostic Impact of Heat Shock Proteins Expression in Patients with Esophageal Cancer: A Meta-Analysis

PURPOSE: Heat shock proteins (HSPs) are highly conserved molecular chaperones. There are various studies that assess the prognostic value of HSPs in patients with esophageal cancer, but the conclusion remains controversial. This is the first meta-analysis study aiming to summarize the evidence on the suitability of HSPs to predict patients' survival. MATERIALS AND METHODS: Searching PubMed, Web of science and Medline until May 31, 2014, data were compared for overall survival in patients with down-regulated HSPs level with those with up-regulated level. We conducted a meta-analysis of 9 studies (801 patients) that correlated HSPs levels with overall survival. Data were synthesized with hazard ratios (HRs). RESULTS: The estimated risk of death was 2.93-fold greater in HSP27 negative patients than HSP27 positive patients [95% confidence interval (CI), 1.12-7.62]. When limited to esophageal squamous cell carcinoma (ESCC), the risk of death in HSP27 negative patients seemed more significant (HR, 3.90; 95% CI, 2.35-6.49). Decreased expression of HSP70 was also associated with worse survival in esophageal cancer (HR, 2.83; 95% CI, 1.90-4.23) and, when limited to ESCC, HR was 3.21 (95% CI, 1.94-5.30). Data collected, however, were not sufficient to determine the prognostic value of HSP90 in patients with ESCC nor esophageal adenocarcinomas (EADC). CONCLUSION: In this meta-analysis, reduced HSP27 and HSP70 expressions were associated with poor survival in patients with esophageal cancer, especially esophageal squamous cell carcinoma.

Expression of Heat Shock Protein 27 and Alpha B Crystallin in the Retina and Optic Nerve of the Chick Embryo / 체질인류학회지

Heat shock protein 27 (HSP27) and alpha B crystallin (aBC) belong to the small heat shock protein (sHSP) family and have similar amino acid sequences. However, no study has compared the distributional patterns of these two sHSPs in the retina and optic nerve. In this study, we compared the spatiotemporal distributions of the expressions of HSP27 and aBC in the developing chick retina and optic nerve. Both HSP27 and aBC were first expressed in the retina and optic nerve at embryonic day 16 (E16). At E20 the expressions of the two proteins were increased in the retina and optic nerve. Double immunofluorescence demonstrated that HSP27 and aBC were expressed in oligodendrocytes of the retina and optic nerve. In addition, HSP27 was also found to be expressed in ganglion cells in the retina. The findings of this study suggest that HSP27 and aBC act to protect ganglion cells and oligodendrocytes during late development of the chick retina and optic nerve.

Research on the role of HSP27 and Fas/Fasl in the invasion and metastasis of triple negative breast cancer / 中国肿瘤临床

Objective:To study the relationship between the expression of heat shock protein 27 (HSP27) in triple negative breast cancer (TNBC) and the clinico-pathological indexes of breast cancer, investigate the correlation between HSP27 and the fatty acid syn-thetase (FAS)/fatty acid synthetase ligand (FASL) of the cell apoptosis system in the Fas/Fasl system, and study the role of HSP27 in the invasion and metastasis of TNBC. Methods:The immunohistochemical S-P method was used to detect the expression of HSP27 and (FAS)/(FASL) in 100 TNBS tissue sampres, 100 non-TNBS tissue sampres, and 50 paraneoplastic tissues. This method was also used to analyze the correlations between the expression of HSP27 and the clinical and pathological indexes of TNBC, as well as be-tween the HSP27 expression and FAS/FASL expression. Results: HSP27 expression was significantly higher in TNBC than in the non-TNBC and paraneoplastic tissues (P0.05), whereas HSP27 expres-sion was correlated with lymph node metastasis, number of nodal metastases, and P53 and Ki67 expression (P<0.05). Conclusion:The overexpression of HSP27 and the expression dysregulation of the FAS/FASL system may play a role in promoting TNBC transfer and invasion, cell proliferation, and poor prognosis.

Silencing of Heat Shock Protein 27 Expression Accelerates Doxazosin-induced Apoptosis in Prostate Cancer Cell Line PC-3

PURPOSE: Heat shock proteins (HSPs) are highly expressed during stress responses and cellular adaptation to environmental changes. One such protein is HSP27, a 27kDa protein that prevents cell death induced by many pro-apoptotic agents. Therefore, the aim of this study was to investigate the correlation between HSP27 expression and apoptosis induced by doxazosin treatment in prostate cancer cell line PC-3. MATERIALS AND METHODS: RT-PCR, Western blotting, and immunocytochemical staining were performed to determine whether HSP27 mRNA and protein are expressed in PC-3 cells. Next, to investigate the effects of doxazosin on apoptosis and HSP27 protein expression in PC-3 cells, the cells were stained using a TUNEL kit (to detect apoptotic cells) and with HSP27 antibody (to assess HSP27 protein expression) 6, 12, 24, and 48h after treatment with 25microM doxazosin. In addition, to determine whether HSP27 mRNA interference accelerates doxazosin-induced apoptosis of PC-3, we knocked down HSP27 with siRNA and then evaluated the rate of apoptosis after doxazosin treatment. RESULTS: HSP27 mRNA and protein were expressed in PC-3 cells. Furthermore, HSP27 mRNA and protein levels increased until 12 hours after 25microM doxazosin treatment, whereas the rate of apoptosis did not increased dramatically. After 12 hours, HSP27 expression decreased and then apoptosis was accelerated. In addition, siRNA-mediated knockdown of HSP27 induce higher apoptosis rate of PC-3 cells even before 12hrs after doxazosin treatment. CONCLUSIONS: By inhibiting apoptosis, HSP27 expression might play an important role in inhibiting progression to castration-refractory prostate cancer and resistance to anti-cancer treatment.