Aloperine Prevents Migration, Invasion, and Adhesion by Upregulating TIMP-4 in Human Bladder Cancer Cells.

BACKGROUND: Aloperine (ALO) is an important active component of quinolizidine alkaloids in Sophora flavescens A and Sophora alopecuroides L, and has effective anticancer activity against multiple cancers. However, the influence and mechanism of ALO on migration, invasion, and adhesion in bladder cancer cells remain unclear. OBJECTIVE: The aim of this study is to determine the anticancer effect of ALO on migration, invasion, and adhesion in bladder cancer cells and to investigate its potential TIMP-4-related mechanism. METHODS: Cell viability, cytotoxicity, wound healing, Transwell invasion, cell adhesion, real-time qPCR, western blot, and ELISA assays were performed to analyze the effect of ALO on migration, invasion, and adhesion in bladder cancer 5637 and UM-UC-3 cells. Furthermore, the anti-TIMP-4 antibody was used to explore the potential effect on ALO-inhibited bladder cancer cells. RESULTS: We have found that ALO significantly suppressed migration, invasion, and adhesion in bladder cancer cells. Furthermore, ALO could downregulate the expression of MMP-2 and MMP-9 mRNAs and proteins, and increase the expression of TIMP-4 mRNA and protein. Moreover, the anti- TIMP-4 antibody reversed the prevention of migration, invasion, and adhesion in ALO-treated bladder cancer cells. CONCLUSION: The data in this study suggest that ALO suppressed migration, invasion, and adhesion in bladder cancer cells by upregulating the expression of TIMP-4.

Matrine induces toxicity in mouse liver cells through an ROS-dependent mechanism.

Matrine is major active component in Sophora flavescens Ait that plays pharmacological activities against inflammation, tumors and virus. However, potential toxicity of matrine and its possible toxic mechanisms have not been carefully studied. The aim of the study is to assess the toxicity of matrine on mouse liver cells and to investigate the potential ROS-associated mechanisms. Mice were randomly divided into three groups: vehicle control (normal saline), low-dose (50 mg/kg), and high dose (100 mg/kg) groups. Mice in each group were intraperitoneally injected with matrine daily for 7 d. The livers were collected for analysis of histopathological changes and HO-1 protein expression. Serum was collected for analysis of aspartate aminotransferase and alanine aminotransferase activities. Mouse liver NCTC cells were treated with matrine for certain time, and cell viability, cytotoxicity, apoptosis, expression of proteins, activities of caspase-3 and caspase-9, and levels of ROS generation, mitochondrial membrane potential, and ATP were examined. Increased activities of AST and ALT in serum, and vacuolar degeneration of cytoplasm in liver tissues were observed after treatment. Suppression of cell viability, increase of cytotoxicity, induction of apoptosis, alteration in the expression of apoptotic-related proteins, and activation of caspase-3 and caspase-9 were shown in matrine-treated NCTC cells. Furthermore, matrine induced ROS generation, and suppressed mitochondrial membrane potential and ATP levels, however, the antioxidant N-acetylcysteine reversed matrine-induced hepatotoxicity and ROS generation. These findings suggested that matrine stimulated the generation of ROS, which was possibly involved in matrine-induced toxicity in mouse liver cells in vitro and in vivo.

Cytochrome P450s regulates aloperine-induced pathological changes in mouse liver and kidney.

Aloperine is a major active component in Sophora alopecuroides L that plays diverse pharmacological properties. Recent studies have indicated the potential effect of aloperine against hypertension and cancers. However, possible toxicity of aloperine has not been carefully studied in vivo. The aim of this study was to assess the effect of intraperitoneal aloperine injection on mouse liver and kidney tissues and to investigate the role of CYP450 genes in aloperine-induced toxicity. 72 BALB/c mice were randomly divided into four groups: vehicle control group (normal saline), low-dose group (4 mg/kg), medium-dose group (8 mg/kg), and high-dose group (16 mg/kg). 18 mice in each group were intraperitoneally injected with aloperine daily for 4 weeks, and were then kept for another 1 or 4 weeks without aloperine treatment. Serum was colleted for analysis of serum biochemical indexes including ALT, AST, BUN and CRE. The liver and kidney were collected for analysis of histopathologic changes and CYP450 expression and activity. Vacuolization of cytoplasm in liver cells, swelling in kidney tubular cells, increased levels of ALT, AST, BUN, and CRE, and alteration in the expression and activity of CYP450 were observed in the high-dose group after 4 weeks of treatment. However, all aloperine-induced damages were recovered to a certain degree after maintained without aloperine for 1 week, and fully recovered after maintained without aloperine for 4 weeks. These findings suggested that aloperine regulated the expression of CYP450, which was possibly involved in aloperine-induced reversible toxicity in mouse liver and kidney tissues.

Diosmetin Induces Apoptosis by Downregulating AKT Phosphorylation via P53 Activation in Human Renal Carcinoma ACHN Cells.

BACKGROUND: Diosmetin (DIOS) is the aglycone of the flavonoid glycoside, diosmin, derived naturally from the leaves of the legume, Olea europaea, and Acacia farnesiana. It has potent anticancer activity against multiple forms of cancers. However, the role of DIOS in renal carcinoma and its mechanism of action remain unclear. OBJECTIVE: The purpose of this study is to investigate the effect of DIOS on cell viability and apoptosis in renal carcinoma cells and explore the possible mechanism of action. METHODS: Cell viability, cytotoxicity, caspase activity, apoptosis, and expression of apoptotic related proteins were analyzed in renal carcinoma ACHN cells. RESULTS: The results showed that DIOS inhibited the cell viability, and induced cytotoxicity and apoptosis in ACHN cells. Furthermore, DIOS increased expression of p53 mRNA and proteins, and downregulated phosphorylation of the phosphoinositide 3-kinase and protein B kinase (PI3K/AKT). In addition, it was observed that the anticancer effect of DIOS was significantly enhanced by the p53 activator, but inhibited by the p53 inhibitor. CONCLUSION: Our data suggested that DIOS induced apoptosis in renal carcinoma ACHN cells by reducing AKT phosphorylation through p53 upregulation.

Aloperine Induces Apoptosis by a Reactive Oxygen Species Activation Mechanism in Human Ovarian Cancer Cells.

BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy worldwide with poor prognosis owing to chemotherapy resistance and cancer relapse. Hence, there is an urgent need to develop novel anticancer agents against ovarian cancer. OBJECTIVE: The aim of this research is to investigate the possible anticancer activity of aloperine, an active ingredient from a traditional Chinese medicine Sophora alopecuroides, and to explore the possible Reactive Oxygen Species (ROS)-related mechanism. METHODS: Cell viability, cytotoxicity, apoptosis, ROS generation, and oxidant stress indicators were analyzed. RESULTS: Our results demonstrated that aloperine significantly induced inhibition of cell viability, promoted cytotoxicity and mitochondrial-related apoptosis, and increased ROS generation in ovarian cancer cells. Furthermore, the antioxidant α-lipoic acid reversed apoptosis in aloperinetreated cells. In addition, we identified hydrogen peroxide as the main type of ROS, and the antioxidant catalase suppressed the apoptotic inducing effect of aloperine whereas hydrogen peroxide supplement exacerbated the effect of aloperine in ovarian cancer cells. CONCLUSION: Taken together, our results indicated that aloperine could exert anti-ovarian cancer cell activity through a reactive oxygen species activation mechanism and suggested aloperine as a potential agent against ovarian cancer.

JS-K enhances chemosensitivity of prostate cancer cells to Taxol via reactive oxygen species activation.

The aim of the present study was to investigate the influence of the nitric oxide donor prodrug JS-K (C13H16N6O8) on Taxol-induced apoptosis in prostate cancer cells, and to investigate a potential reactive oxygen species (ROS)-associated mechanism. The effect of JS-K on the anticancer activity of Taxol was assessed in prostate cancer cells; cell viability, colony formation, apoptosis, ROS generation and expression levels of apoptosis-associated proteins were investigated. The function of ROS accumulation in the combined effects of JS-K and Taxol was determined using the antioxidant N-acetylcysteine (NAC) and the pro-oxidant oxidized glutathione (GSSG). The results of the present study demonstrated that JS-K was able to increase Taxol-induced suppression of prostate cancer cell proliferation, apoptosis, ROS accumulation and upregulation of apoptosis-associated proteins. Furthermore, NAC reversed the effect of JS-K on Taxol-induced apoptosis and conversely, the pro-oxidant GSSG exacerbated the effect of JS-K on Taxol-induced apoptosis in prostate cancer cells. In conclusion, JS-K enhances the chemosensitivity of prostate cancer cells to Taxol, via the upregulation of intracellular ROS.

A reactive oxygen species activation mechanism contributes to Sophoridine-induced apoptosis in rat liver BRL-3A cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L., a traditional Chinese herb, has been widely used to treat numerous diseases throughout China. Quinolizidine alkaloids were identified as active components in Sophora alopecuroides L., and Sophoridine (SRI) is the major component in the Quinolizidine alkaloids. AIM OF THE STUDY: To investigate the toxic effects of SRI in rat liver BRL-3A cells and to explore potential ROS-related mechanisms. MATERIALS AND METHODS: Cell viability, cytotoxicity, apoptosis, intracellular generation of ROS, GSH/GSSG ratio and levels of proteins in mitochondria apoptosis pathway were analyzed. RESULTS: Our data indicated that SRI could suppress BRL-3A cells viability in a concentration- and time-dependent manner and increase cytotoxicity, ROS accumulation and cell apoptosis in a concentration-dependent manner. Expressions and activities of apoptotic related proteins were upregulated, whereas expression of Bcl-2 was downregulated after treatment. Furthermore, level of H2O2 was increased, whereas level of Superoxide was not changed after treatment. Moreover, the antioxidant N-acetylcysteine reversed SRI-induced apoptosis and ROS accumulation. CONCLUSION: Our data suggest that SRI promotes rat liver BRL-3A cells apoptosis by increasing intracellular ROS accumulation.

JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

PURPOSE: Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. METHODS: The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. RESULTS: We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. CONCLUSIONS: JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

JS-K, a nitric oxide pro-drug, regulates growth and apoptosis through the ubiquitin-proteasome pathway in prostate cancer cells.

BACKGROUND: In view of the fact that JS-K might regulate ubiquitin E3 ligase and that ubiquitin E3 ligase plays an important role in the mechanism of CRPC formation, the goal was to investigate the probable mechanism by which JS-K regulates prostate cancer cells. METHODS: Proliferation inhibition by JS-K on prostate cancer cells was examined usingCCK-8 assays. Caspase 3/7 activity assays and flow cytometry were performed to examine whether JS-K induced apoptosis in prostate cancer cells. Western blotting and co-immunoprecipitation analyses investigated JS-K's effects on the associated apoptosis mechanism. Real time-PCR and Western blotting were performed to assess JS-K's effect on transcription of specific AR target genes. Western blotting was also performed to detect Siah2 and AR protein concentrations and co-immunoprecipitation to detect interactions of Siah2 and AR, NCoR1 and AR, and p300 and AR. RESULTS: JS-K inhibited proliferation and induced apoptosis in prostate cancer cells. JS-K increased p53 and Mdm2 concentrations and regulated the caspase cascade reaction-associated protein concentrations. JS-K inhibited transcription of AR target genes and down-regulated PSA protein concentrations. JS-K inhibited Siah2 interactions and also inhibited the ubiquitination of AR. With further investigation, JS-K was found to stabilize AR and NCoR1 interactions and diminish AR and p300 interactions. CONCLUSIONS: The present results suggested that JS-K might have been able to inhibit proliferation and induce apoptosis via regulation of the ubiquitin-proteasome degradation pathway, which represented a promising platform for the development of new compounds for PCa treatments.

JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells.

Reactive oxygen species (ROS) are chemical species that alter redox status, and are responsible for inducing carcinogenesis. The purpose of the present study was to assess the effects of the glutathione S transferase-activated nitric oxide donor prodrug, JS-K, on ROS accumulation and on proliferation and apoptosis in human prostate cancer cells. Cell proliferation and apoptosis, ROS accumulation and the activation of the mitochondrial signaling pathway were measured. The results demonstrated that JS-K may inhibit prostate cancer cell growth in a dose- and time-dependent manner, and induce ROS accumulation and apoptosis in a dose-dependent manner. With increasing concentrations of JS-K, expression of pro-apoptotic proteins increased, but Bcl-2 expression decreased. Additionally, the antioxidant N-acetylcysteine reversed JS-K-induced cell apoptosis; conversely, the pro-oxidant glutathione disulfide exacerbated JS-K-induced apoptosis. In conclusion, the data suggest that JS-K induces prostate cancer cell apoptosis by increasing ROS levels.

MicroRNA-200c suppresses cell growth and metastasis by targeting Bmi-1 and E2F3 in renal cancer cells.

The aim of the present study was to evaluate the functions of miR-200c in the regulation of tumor growth and metastasis in renal cancer cells, and to investigate the underlying mechanisms. In this study, miR-200c was up- and downregulated in two renal cancer cell lines, namely ACHN and A498, and the proliferation, colony formation, migration and invasion of the cells were measured. The expression levels of various mRNAs and proteins were then analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. It was found that miR-200c suppressed proliferation, migration and invasion of the renal cancer cells and, conversely, the inhibition of endogenous miR-200c resulted in increased cell proliferation and metastasis. Furthermore, a luciferase reporter assay revealed that miR-200c directly targeted the 3' untranslated regions of the oncogenes B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) and E2F transcription factor 3 (E2F3) mRNAs, reduced the expression of Bmi-1 and E2F3 and regulated the expression of downstream genes, including E-cadherin, N-cadherin, vimentin, p14 and p16. These results indicate a tumor suppressor role for miR-200c in renal cancer cells via the direct targeting of Bmi-1 and E2F3.

Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.

Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect.

MicroRNA-429 suppresses cell proliferation, epithelial-mesenchymal transition, and metastasis by direct targeting of BMI1 and E2F3 in renal cell carcinoma.

BACKGROUND: MicroRNA-429 (miR-429), a short noncoding RNA belonging to the miR-200 superfamily, plays a crucial role in tumorigenesis and tumor progression. It also acts as a modulator of epithelial-to-mesenchymal transition, a cell development regulating process that affects tumor development and metastasis. The aim of this study was to investigate the potential role of miR-429 in regulating growth and metastasis of renal cell carcinoma. METHODS: miR-429 expression was stably up-regulated or down-regulated in the renal cell carcinoma ACHN and A498 cell lines, and cell proliferation and metastasis were assessed. RESULTS: miR-429 overexpression inhibited cell proliferation, colony formation, migration, and invasion. Suppression of endogenous miR-429 promoted cell growth and metastasis. miR-429 was shown to directly target the 3' untranslated regions of B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) and E2F transcription factor 3 (E2F3) transcripts, regulating their expression, as well as that of the downstream epithelial-to-mesenchymal transition markers E-cadherin, N-cadherin, vimentin, p14, and p16. CONCLUSIONS: These results revealed a tumor suppressive role for miR-429 in renal cell carcinoma through directly targeting BMI1 and E2F3.

Clinicopathologic features of renal epithelioid angiomyolipoma: report of one case and review of literatures.

Epithelioid angiomyolipoma (EAML) is a rare renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis complex (TSC). As metastasis of the tumor cells occur early, EAML is considered a potentially malignant tumor type and intrigues further research on it. Under the microscope, we could find the tumor was composed of atypical polygonal cells sheet mixed with classic angiomyolipoma (AML) components such as blood vessels with notable thick vascular walls, smooth muscle-like cells and adipocytes. Immunohistochemical studies showed that epithelioid cells were focally positive for vimentin, melanocytic markers (HMB-45), myoid markers (α-smooth muscle actin), CD34 and CD68; negative for cytokeratin, epithelial membrane antigen, CD10, and S-100. And the Ki67 index showed approximately 3%. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML and discuss its diagnosis, differential diagnosis and the prognosis.

miR-200c inhibits invasion, migration and proliferation of bladder cancer cells through down-regulation of BMI-1 and E2F3.

BACKGROUND: MicroRNA-200c (miR-200c) is one of the short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. It also acts as considerable modulator in the process of epithelial-to-mesenchymal transition (EMT), a cell development regulating process that affects tumor development and metastasis. However, the role of miR-200c in bladder cancer cells and its mechanism has not been well studied. The purpose of this study was to determine the potential role of miR-200c in regulating EMT and how it contributed to bladder cancer cells in invasion, migration and proliferation. METHODS: Real-time reverse transcription-PCR was used to identify and validate the differential expression of MiR-200c involved in EMT in 4 bladder cancer cell lines and clinical specimens. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200c was over-expressed in UMUC-3 and T24 cells using a lentivirus construct, respectively. Protein expression and signaling pathway modulation were validated through Western blot analysis and confocal microscopy, whereas BMI-1 and E2F3, direct target of miR-200c, were validated by using the wild-type and mutant 3'-untranslated region BMI-1/E2F3 luciferase reporters. RESULTS: We demonstrate that MiR-200c is down-regulated in bladder cancer specimens compared with adjacent ones in the same patient. Luciferase assays showed that the direct down-regulation of BMI-1 and E2F3 were miR-200c-dependent because mutations in the two putative miR-200c-binding sites have rescued the inhibitory effect. Over-expression of miR-200c in bladder cancer cells resulted in significantly decreased the capacities of cell invasion, migration and proliferation. miR-200c over-expression resulted in conspicuous down-regulation of BMI-1 and E2F3 expression and in a concomitant increase in E-cadherin levels. CONCLUSIONS: miR-200c appears to control the EMT process through BMI-1 in bladder cancer cells, and it inhibits their proliferation through down-regulating E2F3. The targets of miR-200c include BMI-1 and E2F3, which are a novel regulator of EMT and a regulator of proliferation, respectively.

Dihydromyricetin induces apoptosis and inhibits proliferation in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a life-threatening disease that is known to exhibit a poor prognosis. Therefore, it is important to identify an effective drug therapy for the treatment of HCC. Dihydromyricetin (DHM) is a flavonoid compound, isolated from the classical Chinese herb Ampelopsis grossedentata, which exhibits multiple pharmacological activities, including anticancer effects. In this study, the anticancer effect of DHM was investigated in nine different types of HCC cell lines via cell proliferation and immunoassays, as well as apoptosis detection. Two immortalized normal human liver cell lines were utilized to determine hepatotoxicity. The results revealed that DHM significantly inhibited cell proliferation and induced cell apoptosis in the HCC cell lines. However, DHM exhibited no cytotoxicity to normal human hepatic cell lines. Furthermore, it was found that DHM induced cell apoptosis in a p53-dependent manner. DHM upregulated p53 expression, and the upregulation of p53 increased the levels of the cleaved caspase-3 protein, directly inducing cell apoptosis. These results indicate that DHM is a promising candidate for the treatment of HCC.

microRNA-183 plays as oncogenes by increasing cell proliferation, migration and invasion via targeting protein phosphatase 2A in renal cancer cells.

The aim of this study was to investigate the function of miR-183 in renal cancer cells and the mechanisms miR-183 regulates this process. In this study, level of miR-183 in clinical renal cancer specimens was detected by quantitative real-time PCR. miR-183 was up- and down-regulated in two renal cancer cell lines ACHN and A498, respectively, and cell proliferation, Caspase 3/7 activity, colony formation, in vitro migration and invasion were measured; and then the mechanisms of miR-183 regulating was analyzed. We found that miR-183 was up-regulated in renal cancer tissues; inhibition of endogenous miR-183 suppressed in vitro cell proliferation, colony formation, migration, and invasion and stimulated Caspase 3/7 activity; up-regulated miR-183 increased cell growth and metastasis and suppressed Caspase 3/7 activity. We also found that miR-183 directly targeted tumor suppressor, specifically the 3'UTR of three subunits of protein phosphatase 2A (PP2A-Cα, PP2A-Cß, and PP2A-B56-γ) transcripts, inhibiting their expression and regulated the downstream regulators p21, p27, MMP2/3/7 and TIMP1/2/3/4. These results revealed the oncogenes role of miR-183 in renal cancer cells via direct targeting protein phosphatase 2A.

Effects of granulosa cells on steroidogenesis, proliferation and apoptosis of stromal cells and theca cells derived from the goat ovary.

The aim of this study was to investigate the effect of granulosa cells from small antral follicles on steroidogenesis, proliferation and apoptosis of goat ovarian stromal and theca cells in vitro. Using Transwell co-culture system, we evaluated androgen production, LH responsiveness, cell proliferation and apoptosis and some molecular expression regarding steroidogenic enzyme and apoptosis-related genes in stromal and theca cells. The results indicated that the co-culture with granulosa cells increased steroidogenesis, LH responsiveness and bcl-2 gene expression as well as decreased apoptotic bax and bad expressions in stromal and theca cells. Thus, granulosa cells had a capacity of promoting steroidogenesis in stromal cell and LH responsiveness in cortical stromal cells, maintaining steroidogenesis in theca cells, inhibiting apoptosis of cortical stromal cells and improving anti-apoptotic abilities of stromal and theca cells.