双氢青蒿素对前列腺癌裸鼠种植瘤Bcl-2和Bax表达的调控

目的研究双氢青蒿素(DHA)诱导前列腺癌细胞凋亡作用及其机制。方法采用人前列腺癌PC-3细胞株建立裸鼠种植瘤模型,将20只模型鼠随机平均分为对照组、溶剂(DMSO)组、DHA200μmol/kg体质量组和DHA100μmol/kg体质量组,经13d干预后,电镜观察肿瘤组织形态学表现;免疫组化检测凋亡相关基因Bcl-2、Bax的表达水平;TUNEL法检测肿瘤组织细胞凋亡。结果与对照组及DMSO组比较,DHA治疗组电镜观察肿瘤组织中散在凋亡细胞及凋亡小体;免疫组化检测凋亡相关基因Bcl-2表达减弱、Bax表达增强,差异均有统计学意义(P<0.05);TUNEL检测结果显示肿瘤组织细胞凋亡率明显升高,差异均有统计学意义(P<0.05)。结论DHA具有较强的诱导前列腺癌细胞凋亡作用,这种作用可能是通过下调Bcl-2和上调Bax表达实现的。

Regulatory effects of dihydroartemisinin on Bcl-2 and Bax expression in implanted prostate cancer in nude mice

Objective To investigate dihydroartemisinin(DHA)-induced apoptosis of human prostate cancer cells and the underlying molecular mechanism.Methods Nude mice were implanted with human prostate cancer PC-3 cells to establish tumor-bearing mouse model.Twenty models mice were evenly randomized into four groups:control group,solvent group(DMSO),large dose DHA (200 μmol/kg) group and low dose DHA (100 μmol/kg) group.The implanted tumors were observed on day 13 after drug administration.Morphological changes of PC-3 cells were observed by transmission electron microscope(TEM).The protein expression of apoptosis associated gene Bcl-2 and Bax were examined by immunohistochemical method.Apoptosis was detected by TUNEL assay.Results TEM examination revealed scattered apoptotic cells and apoptotic bodies in tumor tissues of mice in the DHA groups; immunohistochemical examination revealed that the protein expression of apoptosis-associated gene Bcl-2 was decreased and that of Bax was increased in DHA groups(P<0.05).TUNEL staining revealed that the rate of cell apoptosis increased significantly in DHA groups(P<0.05).Conclusion It is demonstrated that DHA has strong effect in inducing apoptosis in human prostate cancer cell line PC-3 in vivo,which might be related to the down-regulation of Bcl-2 and up-regulation of Bax.