Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo
Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo
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DOI：
10.1111/j.1745-7262.2005.00072.x
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发表时间：
2005-12-01
影响因子：
2.9
通讯作者：
Fang, RY
中科院分区：
文献类型：
--
作者：
He, QJ;Yang, B;Fang, RY
目的：研究对吉唑（DL111-IT）对人前列腺癌细胞PC3的体外和体内抗增殖活性，并探讨其可能的分子机制。方法：采用3-(4,5-二甲基亚-zoi，2-yl)-2,5-二苯基溴化四唑（MTT）试剂法和肿瘤异种移植模型检测DL111-IT的细胞杀伤能力。流式细胞术检测细胞周期，Western blotting检测视网膜母细胞瘤（pRb）、细胞周期蛋白依赖性激酶4 （CDK4）和细胞周期蛋白D1的表达。结果：DL111-IT对人雄激素非依赖型前列腺癌细胞PC3有较强的抑制作用。在PC3肿瘤异种移植研究中，DL 111-IT （1.25 mg/kg-20.0 mg/kg）每天1次，连续10天显著抑制肿瘤生长，抑制率为21% ~ 50%。流式细胞术分析显示，DL111-IT可引起PC3细胞株G(1)阻滞，但不引起细胞凋亡。DL111-IT增强了pRb的表达，下调了CDK4和cyclin d1的表达，提示细胞周期调节可能参与了DL111-IT的抗癌特性。结论：DL111-IT通过细胞周期调控途径在体外和体内抑制人雄激素非依赖性前列腺癌细胞PC3的增殖。
Aim: To evaluate the antiproliferative activity of contragestazol (DL111-IT) on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods: The cell killing ability of DL111-IT was measured by the 3-(4,5-dimethylthia-zoi,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma (pRb), cyclin-dependent kinase 4 (CDK4) and cyclin D1, was detected by Western blotting. Results: DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50% cell inhibition (IC50 value) was 9.9 mg/mL In the PC3 tumor xenograft study, DL 111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50%. Flow cytometric analysis indicated that DL111-IT could cause G(1) arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D I expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT. Conclusion: DL111-IT inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.