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Aim To investigate the effect of Salidroside on the focal celebral ischemia/reperfusion injury in rats and its underlying mechanism. Methods Adult male Sprague-Dawley rats, weighing 260-300 g, were ran-domly divided into three groups: sham, MCAO, MCAO+salidroside ( Sal ) groups. The rats were sub-jected to local celebral ischemia reperfusion with su- ture-occluded method. The rats of MCAO +Sal group were treated intraperitoneally with salidroside ( 50 mg ·kg-1 ) for 6 days. Neurological deficit testing was performed with Longa’ s Scale. The mRNA expressions of Neun,Nogo-A,and NgR were detected by RT-qPCR in ischemic brain. The protein expressions of Neun, NGF , BDNF , Nogo-A and NgR were determined by Western blot. Results Compared with MCAO group, salidroside significantly improved the neurological defi-cit,promoted the expressions of Bcl-2,Neun,NGF,BD-NF, and inhibited the expressions of Nogo-A, NgR. Conclusion Salidroside can reduce neurological defi-cit, increase the number of Nissl’ s Body and the ex-pression of Neun, and protect rats against focal cele- bral ischemia/reperfusion injury,which may be accom-plished by increasing the expressions of Bcl-2, NGF, BDNF, and inhibiting the expressions of Nogo-A, NgR.
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A degeneração macular relacionada à idade (DMRI) é uma das maiores causas de redução da capacidade laborativa, devida à perda da visão central e evolução para cegueira legal, impossibilitando inclusive atividades básicas como ler, escrever, cozinhar, dirigir e reconhecer a fisionomia de pessoas. A incidência desta doença vem aumentando significativamente nos últimos anos e são muitas as dúvidas sobre a escolha do tratamento mais adequado. O objetivo desta revisão é apresentar a fisiopatologia da DMRI e discutir as dificuldades do tratamento desta doença, relacionadas principalmente às vias de administração de fármacos e à escolha do procedimento clínico. Neste contexto, o uso da terapia antiangiogênica na DMRI parece ser, atualmente, o tratamento mais eficaz, devido a sua alta especificidade, pois atua de forma direta no desequilíbrio entre os fatores pró e antiangiogênicos. Entretanto, com base nas evidências atuais, o grande desafio para a saúde pública ainda está na prevenção desta doença e em seu diagnostico precoce.
Age-related macular degeneration (AMD) is a leading cause of reduced work capacity due to the loss of central vision and progression to legal blindness, with the subsequent impedance of basic activities such as reading, writing, cooking, driving and recognizing faces. The incidence of AMD has increased significantly in recent years and many questions remain regarding the most appropriate form of treatment. The aim of the present review was to address the pathophysiology of AMD and discuss difficulties in treating the disease, primarily with regard to drug administration routes and the choice of clinical procedure. The use of anti-angiogenic therapy seems to be the most effective treatment for AMD due to its high specificity, acting directly on the imbalance between pro-angiogenic and anti-angiogenic factors. However, current evidence indicates that the major challenge for public health remains the prevention and early diagnosis of AMD.
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Humans , Macular Degeneration/diagnosis , Macular Degeneration/prevention & control , Macular Degeneration/drug therapy , Growth Inhibitors , Cell Death , Public HealthABSTRACT
ObjectiveTo investigate the inhibitory effect of lentivirusly-mediated ObR-siRNA on transplanted MCF-7 human breast cancer cells by intratumoral injection.MethodsA model of subcutaneous implanted tumor was generated through injecting MCF-7 human breast cancer cells into the nude mice.Thirty established mice with MCF-7 breast cancer cells xenograft were divided into 3 groups randomly,and mice in the experimental group were intratumorally injected with ObR-siRNA lentivirus,while the negative control group and blank control group mice were injected with the same dose of negative lentivirus and normal saline.All mice were subcutaneously injected with recombinant human leptin around the tumor site once a day.Tumor size was blindly measured every other day and the mRNA expression and protein expression levels of ObR in each group were determined.ResultsKnockdown of ObR-treated xenografted nude mice with a high leptin microenvironment was successfully established.Local injection of ObR-siRNA lentivirus significantly suppressed the established tumor growth in nude mice(P ＜ 0.01,P ＜0.01 ).Real time-PCR and Western blotting showed that the mRNA and protein expression of ObR was decreased in the ObR-siRNA lentivirus group( P ＜ 0.01,P ＜ 0.01 ).ConclusionsIntratumoral injection of recomhinant ObR-siRNA lentivirus inhibits the growth of MCF-7 cells xenografts in the nude mice,suggesting that ObR might represent a therapeutic target in the genotherapies of human breast cancer.
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Objective To investigate the apoptosis-inducing effect of oridonin combined with valproic acid( VPA)on leukemic cell line HL-60,and study the feasibility of oridonin combined with VPA to be used in clinical practice. Methods Oridonin of 6-12 μmol/L combined with VPA of 0. 5-1 mmol/L were added in exponential growth HL-60 cells respectively. Cell count assays were used to measure the growth inhibitory effect of oridonin combined with VPA or alone. Flow cytometry was used to evaluate apoptosis with Annexin V and propidium iodide (PI) double staining. Results Combined use of oridonin and VPA could synergistically inactivate HL-60 cells,and inhibit the cell proliferation and induce apoptosis in a dose-and time-dependent manner (P < 0.05 ). Conclusion Oridonin has a synergistic effect combined with VPA. Oridonin has a promising prospect in clinical use of leukemia.
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Objective To investigate the effect of arsenic trioxide (ATO) on the growth inhibition of bcr-abl mutant cell lines in vitro and to explore its potential mechanism. Methods The growth inhibition of ATO on bcr-abl wild type cell lines (K562, KBM5 and 32Dp210) and imatinib(IM)-resistant cell lines (K562R, KBM5R, 32Dp210T315I, 32Dp210Q252H, 32Dp210Y253H, 32Dp210M351T and 32Dp210E255K) were measured by trypan blue exclusion. Apoptosis was assayed by AnnexinV and PI staining. Glutathione (CSH) levels were detected by DTNB colorimetry of Glutathione Assay Kit. Results ATO inhibited cell growth in both bcr-abl wild type and IM-resistant mutant type cells in a dose dependent manner. ATO significantly inhibited growth of bcr-abl point mutant cells compared with the corresponding wild type cells, and the IC50 of ATO in mutant cells was lower than that in wild type, while the IC50 in no point mutant cells K562R was not different compared with that in wild type cells K562. The GSH levels in bcr-abl point mutant cells were lower than that in the corresponding wild type cells(P =0.00106-0.0358) , but that in K562 was quite similar with K562R cells(P = 0.315). After depletion of intracellular GSH by using BSO, the growth inhibition of ATO in both bcr-abl point mutant cells and wild type cells was significantly enhanced. Conclusion The growth inhibition of ATO on bcr-abl point mutant cells is remarkably more effective than that on wild type cells, which may be related with intracellular GSH. ATO would be a potential therapeutic select against CML with bcr-abl point mutation including the T315I mutation.
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Inhibitor of growth 2 (INC2 ) is a member of INC family, and cooperates with p53 in regulating cell cycle, apoptosis, and aging. It can also facilitate chromatin remodeling and transcription regulating through histone modifications. Researches suggest that INC2 protein is an important factor in the genesis, metastasis and prognosis of many kinds of tumors. Resent studies indicate that INC2 can not be simply classified as oncogene or tumor suppressor. At present, the function of INC2 in tumorigenesis and tumor development involves interaction with varied molecules, but the mechanisms remain largely unknown, which still require further investigation.
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Objective To investigate ING2 expression in normal gastric tissue,gastric carcinoma and precancerous lesions, and to explore correlation between ING2 expression and the carcinogenesis and progression of gastric carcinoma and the clinicopathological signficance as well as the correlation between ING2 and raP53 protein. Methods The expression of ING2 was measured by PV9000 two-step immunohistochemical staining. In total, 188 gastric cancer(GC), 128 matched normal gastric mucosa,35 chronic atrophic gastritis (CAG), 87 intestinal metaplasia (IM) and 36 dysplasia (DYS) samples were analyzed. Expression of mP53 was measured in 40 samples from the 188 gastric carcinomas mentioned above. Results Positive ING2 expression was significantly more frequent in CAG (74.29%) ,IM (91.95%) ,DYS (75.0%) and GCs (70.21%) than in normal gastric mucosa (36.72% ,P ＜0.05). Among GCs, ING2 expression varied by Lanren's classification. A significantly higher rate of positive ING2 expression was observed in intestinal type GCs (80. 56%) than in diffuse (64.49%) and mixed (55.56%, P ＜ 0.05) type GCs. Furthermore, positive ING2 expression was significantly more frequent in well-to-moderately differentiated adenocarcinoma(80. 60%) than in poorly differentiated adenocarcinoma (62. 62%, P ＜ 0. 05). No correlation was found between ING2 expression and mP53 expression in GC (P ＞ 0. 05). Over-expression and mislocalization of ING2 may be involved in the development of CC, especially intestinal-type GC. Further investigations are needed to explore the relevant molecular mechanism.
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AMPK (AMP-activated protein kinase) is highly conserved in eukaryotes, where it functions primarily as a sensor of cellular energy status. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumor cells. In this study, quercetin activated AMPK in MCF breast cancer cell lines and HT-29 colon cancer cells, and this activation of AMPK seemed to be closely related to a decrease in COX-2 expression. The application of a COX-2 inhibitor or cox-2(-/-) cells supported the idea that AMPK is an upstream signal of COX-2, and is required for the anti-proliferatory and pro-apoptotic effects of quercetin. The suppressive or growth inhibitory effects of quercetin on COX-2 were abolished by treating cancer cells with an AMPK inhibitor Compound C. These results suggest that AMPK is crucial to the anti-cancer effect of quercetin and that the AMPK-COX-2 signaling pathway is important in quercetin-mediated cancer control.
Subject(s)
Humans , AMP-Activated Protein Kinases/antagonists & inhibitors , Anticarcinogenic Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclooxygenase 2/genetics , Cyclooxygenase 2 Inhibitors/pharmacology , Enzyme Activation , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Quercetin/pharmacologyABSTRACT
OBJECTIVE To study the effect of Meloxicam on the growth inhibition and apoptosis induction in nasopharyngeal carcinoma CNE-1 cell line.METHODS Technique of cell culture and randomized blank-contrast design were used.The degree and dose-dependency of Meloxicam which induced growth inhibition and apoptosis in CNE-1 cell line were observed by MTT method,AO+EB straining and flow cytomethy.COX-2 were determined using cell immunoflurorescence.RESULTS MTT assay showed that Meloxicam inhibite the growth of CNE-1 cells.AO+EB straining showed partial cells presented characteristic morphological changes of apoptosis.Flow cytometry analysis showed that treating CNE-1 cells with Meloxicam increase the percentage of apoptosis cells.Cell immunoflurorescence revealed that the COX-2 expression was decreased.CONCLUSION Meloxicam could significantly inhibit the growth and induce apoptosis of CNE-1 cells.Apoptosis of tumor cells is closely associated with down regulation of the ratio of COX-2.
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SC-560, a strucutral analogue of celecoxib, induces growth inhibition in a wide range of human cancer cells in a cyclooxygenase (COX)-independent manner. Since SC-560 suppresses the growth of cancer cells mainly by inducing cell cycle arrest, we sought to examine the role of p21CIP1, a cell cycle regulator protein, in the cellular response against SC-560 by using p21(+/+)and p21(-/-)isogenic HCT116 colon carcinoma cells. In HCT116 (p21(+/+)) cells, SC-560 dose-dependently induced growth inhibition and cell cycle arrest at the G1 phase without significant apoptosis induction. SC-560-induced cell cycle arrest was accompanied by upregulation of p21CIP1. However, the extent of SC-560-induced accumulation at the G1 phase was approximately equal in the p21(+/+)and the p21(-/-)cells. Nonetheless, the growth inhibition by SC-560 was increased in p21(-/-)cells than p21(+/+)cells. SC-560-induced reactive oxygen species (ROS) generation did not differ between p21(+/+)and p21(-/-)cells but the subsequent activaton of apoptotic caspase cascade was more pronounced in p21(-/-)cells compared with p21(+/+)cells. These results suggest that p21CIP1 blocks the SC-560-induced apoptotic response of HCT116 cells. SC-560 combined with other therapy that can block p21 CIP1 expression or function may contribute to the effective treatment of colon cancer.
Subject(s)
Humans , Reactive Oxygen Species/metabolism , Pyrazoles/pharmacology , Mutation , Immunoblotting , HCT116 Cells , Genotype , Flow Cytometry , Dose-Response Relationship, Drug , Cyclooxygenase Inhibitors/pharmacology , Cyclin-Dependent Kinase Inhibitor p21/genetics , Colonic Neoplasms/genetics , Cell Survival/drug effects , Cell Proliferation/drug effects , Cell Differentiation/drug effects , Cell Cycle Proteins/metabolism , Cell Cycle/drug effects , Apoptosis/drug effects , Antineoplastic Agents/pharmacologyABSTRACT
Objective To assess the effect of recombinant human leukemia inhibitory factor (rhLIF) on mouse embryo development in vitro Methods Mice were randomly divided to three groups, one in vivo control (group Ⅰ) and two in vitro (group Ⅱ and Ⅲ) Mice were sacrificed at 116 120 hours (group Ⅰ) and 44-48 hours (group Ⅱ and Ⅲ) subsequent human chorionic gonadotropin (hCG) injection Two cell embryos (group Ⅱ and Ⅲ) and blastocysts (group Ⅰ) were obtained Embryos in group Ⅱwere cocultured with human tubal fluid (HTF) + 10% human serum and in group Ⅲ with HTF + 10% human serum+rhLIF (1 000 U/ml) The number of embryo in different stage was recorded and compared Results Embryo in four, eight cell and morula was noted in group Ⅱ and Ⅲ, 87 7% versus 91 2% and 75 0% versus 85 4% respectively There was no significant difference. However, further embryo development to the blastocyst, expanded blastocyst, and hatching blastocyst in group Ⅱ (48 1%, 32 1% and 18 4%) was lower than that in group Ⅲ (82 3%, 59 7% and 36 3%) There was no difference between blastocyst in group Ⅰ and group Ⅲ (86 0% vs 82 3%). Conclusion RhLIF does not provide obvious stimulation in early mouse embryo, however, rhLIF can promote the growth, differentiation, and hatching of preimplantion blastocyst
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Objective To study the effects of angiogenesis inhibitor SU5416 on the growth and metastasis of pancreatic cancer in SD rat model. Methods Dimethylbenzanthracine (9 mg) (DMBA),was implanted into the parenchyma of Sprague Dawley rat pancreas to induce pancreatic cancer. Rats with established pancreatic carcinoma were randomly divided into 4 groups (15 rats each) to receive every the other day for consecutive 13 weeks before sacrifice peritoneal cavity injection of: Normal saline (control),5-fluorouracil 30 mg?kg -1 (5-Fu group),SU5416 16 mg?kg -1 (SU5416 group),and both 5-Fu and SU5416(combined treatment group). Tumor weight,inhibition rates,intratumoral microvessel density (MVD),apoptotic index (AI) and metastasis were evaluated. Results Tumor weight was (1.15?0.21) g,(0.68?0.42) g,(0.31?0.11) g,(0.19?0.06) g respectively;the inhibition rate was 0,48%,80%,85% respectively;the intratumoral microvessel density (MVD) was (12.3?3.2),(11.4?3.8),(2.1?1.5),(1.8?1.1) respectively;The apoptotic index (AI) was (2.64?1.86)%,(5.71?3.14)%,(13.21?4.26)%,(21.12?7.15)% respectively. Peritoneal metastasis was significantly less severe in 5-Fu group,SU5416 group and combined group than that in control group(83% versus 46%,25% and 0) ( P
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AIM: To investigate the effect of sucking porcine liver extracts (LE) and doxorubicin (DXR) on BEL-7402 hepatoma cells in the renal capsulae of BALB/c nude mice. METHODS: Histo-cellular morphology, mitotic counting, ultrastructural observation and in situ DNA labeling apoptotic detection were performed. RESULTS: Both LE and DXR can apparently inhibit the tumors' growth and induce the apotosis of hepatoma cells. LE exerted no apparent effect on the hepatoma cell mitosis, but DXR inhibited it. Electron-microscopic observations showed LE can induce the hepatoma cells to apoptosis. CONCLUSIONS: LE can induce the hepatoma cells to apoptosis, but has no apparent effect of their differentiation and proliferation. DXR can not only induce the hepatoma cells to apoptosis and inhibit their growth, but also can promote their differentiation.
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0.05). While serum pregesterone, hCG levels in inevitable group were (33.1?19.6) nmol/L, (10.3?3.2) kU/L respectively. Compared with normal early pregnancy and threatened abortion group, the levels of serum pregesterone and hCG reduced significantly ( P
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Objective To determine the effects of lensspecific overexpression of OSM on the eye development. Methods A truncated mouse OSM cDNA (661 bp) was linked to the ?A-crystallin promoter. Transgenic mice were characterized by routine histological and immunohistochemical techiniques. TUNEL assays were used to detect cell death. The mRNA expression of caspase-3 was detected by in situ hybridization, Rabbit anti-cleavage caspase-3 antibody was used to detect active capase-3. Results At embryonic day (E) 14.5 and 17.5, expression of the OSM transgenic protein was detected specifically in lens fiber cells. The onset of retinal degeneration in the mid portion of the transgenic retinae was observed started from E17.5. By the time of birth 50% or more of the retinal cells were missing. The OSM transgenic retinal cells underwent apoptosis indicated by TUNEL assays. Most strikingly, activation of caspase-3 protein were observed throughout the transgenic retinas. Conclusions Lens-specific overexpression of OSM activate caspase-3, leading to abnormal eye development, apoptosis and widespread retinal degeneration.
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Objective To investigate whether difluromethylornithine (DFMO) can be used in the treatment of human leukemia. Methods The cell proliferation was detected by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)] assay after treatment of human lymphocyte Jurkat cells by DFMO (0 to 10 mmol/L) for 24 to 72 h. Enzyme activity of spermine oxidase (SMO) and acetylpolyamine oxidase (PAO) was determined by chemiluminesence assay. DNA fragmentation assay was used to evaluate cell apoptosis. Fluorescent dye assay was performed to determine the changes in mitochondrial membrane potential. Western blotting was used to determine Bax content. Casepase-3 enzyme activity was measured by spectrophotometric method. Results DFMO treatment inhibited the proliferation of Jurkat cells significantly in a dosage- and time-dependent manner (P