德士康对前列腺癌激素非依赖型细胞株细胞周期的抑制作用  

Effect of Chinese herbal medicine-Deshikang on cell cycle arrest in androgen- independent prostate carcinoma cell lines

作　　者：杜广[1] 郭鹏[2] 郭剑明[1] 张正望[1] 张永康[1] 沈波 刘飞 

机构地区：[1]复旦大学上海医学院附属中山医院泌尿外科,上海200032 [2]复旦大学卫生部糖复合物重点实验室 [3]上海兆维科技发展有限公司实验室

出　　处：《肿瘤》2005年第2期136-139,共4页Tumor

摘　　要：目的　探讨中草药混合制剂德士康(暂定名)对雄激素非依赖型前列腺癌细胞株PC -3、DU145 细胞周期的抑制作用和机制。方法　MTT法检测用药后细胞增殖的改变,流式细胞仪(FCM)测定细胞周期的改变,Western blot方法分析细胞周期相关蛋白表达的改变。结果　德士康可抑制PC- 3、DU145 细胞的生长,PC- 3、DU145 分别主要受阻于G1 期和G2/M期。用药组p16lnk4a蛋白表达增高,Rb磷酸化蛋白表达降低,伴有非磷酸化Rb蛋白的相应增多;而p21waf1、p27Kip1 和细胞周期蛋白cyclin D1的表达均无明显改变。结论　德士康可能是通过影响p16lnk4a蛋白的表达,改变细胞周期蛋白依赖蛋白激酶的活性,最后作用于Rb,抑制其磷酸化而发挥作用,从而抑制PC -3、DU145细胞的生长,具有应用于临床治疗的前景。Objective To study the action of a herbal mixture n amed Deshikang on the inhibition of the cell cycle of androgen independent prost ate adenocarcinoma cell lines:PC-3 and DU145, as well as its mechanism. Methods The growths of PC-3 and DU145 were showed by MTT. The cell r atio in the different stages of the cell cycle of PC-3 and DU145 were determine d by flow-cytometry. The expressions of cell cycle related proteins were analyz ed with their monoclonal or polyclonal antibodies after Western blot. Re sults The growths of PC-3 and DU145 was inhibited by Chinese herbs. Th e cell cycle of PC-3 cells was mainly blocked at the G1 stage, while that of DU 145 cells were blocked at both G 1 and G 2/M stages. The expression of p16 lnk4a, a cell cycle inhibitory protein, was elevated and the phosphory lated RB protein was decreased in the cells treated with Deshikang as compared w ith the non-treated control cells. However, the expressions of p21 waf1,p2 7 Kip1 and cyclin D1 proteins were not altered. Conclusions Herbal mixture Deshikang induces the growth inhibitions of PC-3 and DU145 by cell cycle arrest, resulting from the up-regulation of p16 lnk4a expressi on, which in turn inhibited the activity of cyclin dependent kinase (CDK) and re duced the phosphorylation of RB. Therefore, Deshikang is expected to use in the clinical treatment of androgen independent prostatic adenocarcinoma.

关 键 词：前列腺肿瘤 细胞周期 中草药 PC-3细胞 DU145细胞 

分 类 号：R737.25[医药卫生—肿瘤] R73-36[医药卫生—临床医学]