The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells wer...The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of mye- loid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated antiapoptotic proteins in androgen-independent prostate cancer cells in vitro.展开更多
Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were e...Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.展开更多
目的研究参附注射液(SF)对人前列腺癌PC-3细胞增殖的影响及可能机制。方法实验设立空白对照组和参附注射液不同浓度组,用MTT方法检测细胞增殖,碘化丙碇(PI)染色流式细胞术检测细胞周期分布,RT-qPCR检测细胞周期蛋白Cyclin D、Cyclin E m...目的研究参附注射液(SF)对人前列腺癌PC-3细胞增殖的影响及可能机制。方法实验设立空白对照组和参附注射液不同浓度组,用MTT方法检测细胞增殖,碘化丙碇(PI)染色流式细胞术检测细胞周期分布,RT-qPCR检测细胞周期蛋白Cyclin D、Cyclin E mRNA的表达。结果与空白对照组比较,作用24,48,72 h后,参附注射液100μL/mL对PC-3细胞均有明显的增殖抑制作用(P<0.05),细胞增殖指数下降,Cyclin D、Cyclin E mRNA的表达量均明显降低(P<0.05)。结论参附注射液可以抑制PC-3细胞增殖,作用机制可能与降低Cyclin D、Cyclin E mRNA表达相关。展开更多
基金We thank Mr Wen-Tong Meng and Mr Ji-Long Gou (Stem Cell Research Laboratory, West China Hospital, Sichuan University, Chengdu, China) for technical assistance with the flow cytometry. We also thank BioMed Proofreading for their editing work. This work was supported by grants to Prof. Hao Zeng and Dr Rui Huang from the National Natural Science Foundation of China (NSFC 30700977 and 30600153).
文摘The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of mye- loid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated antiapoptotic proteins in androgen-independent prostate cancer cells in vitro.
文摘Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.
文摘目的研究参附注射液(SF)对人前列腺癌PC-3细胞增殖的影响及可能机制。方法实验设立空白对照组和参附注射液不同浓度组,用MTT方法检测细胞增殖,碘化丙碇(PI)染色流式细胞术检测细胞周期分布,RT-qPCR检测细胞周期蛋白Cyclin D、Cyclin E mRNA的表达。结果与空白对照组比较,作用24,48,72 h后,参附注射液100μL/mL对PC-3细胞均有明显的增殖抑制作用(P<0.05),细胞增殖指数下降,Cyclin D、Cyclin E mRNA的表达量均明显降低(P<0.05)。结论参附注射液可以抑制PC-3细胞增殖,作用机制可能与降低Cyclin D、Cyclin E mRNA表达相关。