Over-expression of programmed cell death 5 gene enhances chemosensitivity of brain glioma cells to temozolomide / 中国肿瘤生物治疗杂志

@# Objective: To explore the role of tumor suppressor gene programmed cell death 5 gene (PDCD5) in the growth and temozolomide (TMZ) sensitivity of brain glioma cells. Methods:Atotal of 116 patients with cerebral glioma admitted to the Department of Neurosurgery, First Clinical Hospital of Jilin University from January 2009 to December 2014 were enrolled in this study. QPCR, WB and immunohistochemistry method were used to detect the mRNAand protein expressions of PDCD5 in glioma cell lines (U87, U251), U87 cell line with stable PDCD5 expression (U87-PDCD5), glioma cells with si-PDCD5 transfection and primary cerebral glioma tissues, respectively. MTT assay was used to detect the effect of over-expression or knockdown of PDCD5 on the growth and TMZ-sensitivity of glioma cells. The subcutaneous tumor-bearing model of glioma cell line U87 was established in nude mice, and then the experimental mice were randomly divided into control group, TMZ group, PDCD5 group and TMZ+exogenous PDCD5 recombinant expression vector group.After 20 days, the animals were sacrificed by cervical dislocation and the tumor tissue was excised to measure the tumor volume and weigh. The expression of PDCD5 in tumor tissues was detected by qPCR and WB methods, and the effects of PDCD5 combined with TMZ on the growth of gliomas were also analyzed. Results: The relative mRNA and protein expressions of PDCD5 in U87 cells were significantly lower than those in U251 cells (both P<0.05), and the mRNA and protein expressions of PDCD5 in high level glioma tissues were significantly lower than those in low level tissues (all P<0.05). The sensitivity of U87-PDCD5 cells and U251 cells to TMZ was higher than that of U87 cells (all P<0.05). The sensitivity of cells to TMZ in U87-PDCD5-siRNA group and U251siRNA group was significantly lower than that of the control group (both P<0.05). The tumor volume and weigh to fnudemicexenografts were compared,and the results showed control group>TMZ group>PDCD 5group>combined group(allP<0.05);however, the mRNA and protein expressions of PDCD5 in the transplanted tumor tissues of each group showed the opposite trend (all P<0.05). Conclusion: PDCD5 over-expression can enhance the chemosensitivity of braingliomato the chemotherapy drug TMZ, while silencing of PDCD5 expression exertsthe opposite effect.The combination of PDCD5 and TMZ can better inhibit the growth of xenografts in nude mice.

Programmed cell death 5 transgenic mice attenuates adjuvant induced arthritis by 2 modifying the T lymphocytes balance

BACKGROUND: Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice. RESULTS: In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4. CONCLUSIONS: Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.

Clinical Significance of Programmed Cell Death 5 Protein in Serum of Patients with Lung Cancer / 中国药房

OBJECTIVE:To investigate clinical significance of programmed cell death 5 (PDCD5) protein in serum of pa-tients with lung cancer. METHODS:80 lung cancer inpatients were selected from the First Affiliated Hospital of Shihezi University School of Medicine(hereinafter referred to asour hospital)as lung cancer group;60 healthy volunteers were selected from our hospital at the same period as normal group. ELISA was used to test the expression of PDCD5 protein,and the relationship of PDCD5 protein with clinical pathological features of lung cancer patients were analyzed. RESULTS:The expression of PDCD5 pro-tein in normal group was significantly higher than lung cancer group,with statistical significance (P0.05);it was de-creased as the decrease of tumor differentiation degree,with statistical significance(P<0.05). The expression of PDCD5 protein in patients with carcinoembryonic antigen(CEA)<5.6μmol/L was significantly higher than those with CEA≥5.6μmol/L;the expres-sion of PDCD5 protein in patients with cytokeratin 19 soluble fragment (CYFRA21-1)<5.6 μmol/L was significantly higher than those with CYFRA21-1≥5.6 μmol/L,with statistical significance(P<0.05). The expression of PDCD5 protein in patients with Ⅰ-Ⅱ stage lung cancer was significantly higher than Ⅲ-Ⅳ stage lung cancer patients;the expression of PDCD5 protein in patients without distant metastasis was significantly higher than those with distant metastasis. The expression of PDCD5 protein was in de-creasing as the increase of the number of metastasis site,with statistical significance(P<0.05). CONCLUSIONS:PDCD5 protein in serum of patients with lung cancer shows low expression level,which is related to tumor differentiation degree,tumor marker level as CEA and CYFRA21-1,tumor stage and distant metastasis,etc. The detection of PDCD5 protein may contribute to clinical diagnosis of lung cancer.

Effects of PDCD5 on hypoxia/reoxygenation-induced autophagy and apoptosis of cardiomyocytes / 中国病理生理杂志

AIM:To investigate the influence of programmed cell death 5 (PDCD5) on apoptosis and autoph-agy in the cardiomyocytes exposed to hypoxia/reoxygenation ( H/R) and its potential mechanism .METHODS:H9c2 cells were exposed to H/R.PDCD5 was downregulated by RNA interference .The cell viability was measured by MTT assay . TUNEL assay was used to detect cell apoptosis .The mRNA and protein levels were determined by RT-qPCR and Western blot.RESULTS:The expression of PDCD5 was upregulated in the cardiomyocytes after H/R injury.Furthermore, H/R injury obviously reduced the cell viability and enhanced the apoptosis and autophagy of the cardiomyocytes .However, knockdown of PDCD5 increased the cell viability , and attenuated H/R-induced apoptosis , accompany with reduction of Bax and augment of Bcl-2 expression .Additionally , silencing PDCD5 markedly inhibited H/R-induced autophagy by regulating the expression of LC3-II/LC3-I and beclin-1.Moreover, downregulation of PDCD5 suppressed NF-κB signaling by redu-cing the protein level of p-P65.CONCLUSION: Silencing PDCD5 suppresses H/R-induced H9c2 cells apoptosis and autophagy by blocking NF-κB signaling pathway .The result indicates a new strategy for the prevention and treatment of myocardial I/R injury.

Treatment of paclitaxel combined with oxaliplatinchemotherapy to the non-small cell lung cancer mouse model / 基础医学与临床

Objective To investigate the therapeutic effect of paclitaxel plus oxaliplatin chemotherapy to the transplanted non-small cell lung cancer of nude mice and the effect to the apoptosis protein expression of PDCD5 and XIAP with mice model.Methods A tumor-bearing mice were randomly divided into blank group, normal saline group, oxaliplatin group, paclitaxel group, paclitaxel plus oxaliplatin group.The gene expression of PDCD5 and XIAP was assayed by real-time quantitative PCR(q-PCR).The apoptosis related PDCD5 and XIAP protein were detected by Western blot.Finally, the tumor weight of each group was measured for statistical analysis.ResultsThe mRNA expression of PDCD5 was highest and the gene expression of XIAP was lowest in paclitaxel plus oxaliplatin group(P<0.01).The expression of PDCD5 protein was highest and the expression of XIAP protein was lowest in paclitaxel plus oxaliplatin group (P<0.01).Finally, compare the tumor weight of each group, paclitaxel plus oxaliplatin group has the least mass(P<0.01).Conclusions Paclitaxel plus oxaliplatin group chemotherapy significantly increases PDCD5 expression and reduce XIAP expression.Meanwhile, paclitaxel plus oxaliplatin chemotherapy can significantly reduce the tumor weight of happened non-small cell lung cancer.

Expression of survivin and programmed cell death 5 in mucoepidermoid carcinoma and their clinical sig-nificance / 实用口腔医学杂志

Objective:To investigate the expression of Survivin and programmed cell death 5(PDCD5)protein in mucoepidermoid carcinoma(MEC).Methods:Survivin and PDCD5 were detected by immunohistochemical staining in 20 cases of normal parotid tis-sue(group A),40 cases of pleomorphic adenoma(group B)and 45 cases of MEC tissues(group C).Results:The positive expres-sion ratio of Survivin in group A,B and C was 10.0%,27.5% and 55.6% respectively(χ2 =14.556,P <0.01),while that of PD-CD5 was 85%,65% and 33.3% respectively (χ2 =17.439,P <0.01).The expression of survivin or PDCD5 was related with dif-ferentiation,lymph node metastasis and TNM staging of MEC.Survivin and PDCD5 showed a negative correlation in MEC(χ2 =4.500,P =0.034,γs =-0.316).Conclusion:Survivin over-expression and PDCD5 down-expression may play a role in the de-velopment and progress of mucoepidermoid carcinoma.

Clinical relativity of PDCD5 with tumor / 国际肿瘤学杂志

Programmed cell death 5(PDCD5)is a new kind of programmed cell death regulation and control gene. PDCD5′s expression is widespread,and evolution is conservative. PDCD5 has the effect of promo-ting a wide variety of tumor cells to apoptosis and inhibiting proliferation,such as lung cancer,liver cancer et al. Several laboratories′ discoveries show that PDCD5′s expression is significantly decreased when in some dis-ease cases,especially in tumor cases. PDCD5,which is related to the clinical relevance of the tumor,has a great clinical value of discovering,diagnosis and treatment of the tumor.

Transfection of PDCD5 plasmid for promoting cisplatin-induced A549 cells apoptosis / 重庆医学

Objective To observe the role of programmed cell death 5(PDCD5) gene combined with cisplatin for inducing the ap-optosis of human lung adenocarcinoma A549 cells and to investigate its possible mechanism .Methods The PDCD5 recombinant plas-mid was transiently transfected into A549 cells by lipofectamine .Its transfection efficiency was detected by RT-PCR .The expressions of trasfected PDCD5 protein ,Bcl-2 and Survivin protein were examined by Western bolt .The apoptosis of A549 cells by single PDCD5 and its combination with cisplatin was measured by the MTT method and the flow cytometry .Results PDCD5 recombinant plasmid was transfect into A549 cells successfully .The Western blot results showed that the expression of PDCD5 protein in the transfection recombinant plasmid group was higher than that in the blank control group and the transfection empty plasmid group ,while the expres-sion of Bcl-2 and Survivin protein was lower than that in the other two groups ,the difference was statistically significant (P<0 .05) . The MTT and flow cytometry results demonstrated that the cell apoptosis rate in the transfection recombinant plasmid group was higher than that in the blank control group and the transfection empty plasmid group (P<0 .05) .Conclusion PDCD5 gene may pro-mote cisplatin induced A549 cells apoptosis .

Expression of programmed cell death 5 in endometrial adenocarcinoma and its clinical significance / 中国基层医药

Objective This study was designed to investigate the relationship between programmed cell death 5 (PDCD5) and endometrial carcinoma .Methods 60 tissue samples of endometrial carcinomas ,40 normal proliferative endometrium tissues and 28 endometrial atypical hyperplasia tissues were obtained from patients who underwent operation.The expression of PDCD5 was detected by Real-time PCR and immunohistochemical analysis . Results In normal proliferative endometrium , atypical hyperplasia tissues and endometrial carcinoma , the PDCD5 mRNA was gradually decreased[(1.21 ±0.16),(0.83 ±0.07),(0.42 ±0.02),F=5.637,P0.05). Conclusion PDCD5 might become a potential molecular marker of early diagnosis of endometrial carcinoma .

Correlation of PDCD5 and Apoptosis in Hair Cells and Spiral Ganglion Neurons of Different Age of C57BL/6J Mice / 华中科技大学学报（医学）（英德文版）

This study examined the expression pattern of programmed cell death 5 (PDCD5) in cochlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3,6,9 or 12 months).PDCD5 expression was detected by using immunohistochemistry,real-time PCR and Western blot.Morphological change of the cochleae was also evaluated by using immunoassay.The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice,as well as gradually increased apoptosis of cochlear hair cells and SGNs.In addition,we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing.It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs,and thereby plays a role in the pathogenesis of presbycusis.Thus,PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.

Glucagon-like peptide-1 reverses the cytokines-induced expression of programmed cell death 5 gene in pancreatic ?-cells / 中国糖尿病杂志

Objective To investigate the effects of glucagon-like peptide-1(GLP-1)on the expression of apoptosis-related molecules including programmed cell death 5(PDCD-5)gene in pancreatic ? cells induced by proinflammatory cytokines.Methods Mouse islet ?-cell line NIT-1 was incubated for 24 h with cytokine mixture(Mix)in the absence or presence of GLP-1.The apoptotic cells were assayed by flow cytometry after stained with annexin V-FITC and propidium iodide(PI).The expressions of PDCD5,Fas,and caspase 3 were detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blot.Results The number of both annexin V single positive cells and annexin V/PI double positive cells significantly increased in the cells treated with 30 U/mL interleukin-1?(IL-1?)+ 100 U/mL interferon-?(IFN-?)+ 100 U/mL tumor necrosis factor-?(TNF-?).The expressions of PDCD5,Fas,and caspase 3 at both mRNA and protein levels were upregulated in the cells exposed to the cytokines.The above-mentioned effects of the cytokines were reversed by 10 nmol/L of GLP-1.Conclusion These data show that the proinflammatory cytokines cause pancreatic ? cell apoptosis via activation of PDCD5 signal pathway and that GLP-1 inhibits the upregulation of PDCD5 expression and the subsequent event of apoptosis induced by the cytokines.