新型青蒿素衍生物SM1052抗人子宫内膜癌RL95-2肿瘤活性研究  

Anti-tumor activity of SM1052,a novel artemisinin derivative,in the human endometrial carcinoma RL95-2 cells

作　　者：周洁芸[1] 谢淑武[1] 张瑜[2] 李国停 桂幼伦[1] 李英[2] 朱焰[1] 

机构地区：[1]上海市计划生育科学研究所生殖药理组,国家卫生与计划生育委员会计划生育药具重点实验室,上海生殖健康药具工程技术研究中心,上海200032 [2]中国科学院上海药物研究所,上海201203 [3]复旦大学,上海200032

出　　处：《中国新药杂志》2014年第12期1431-1437,共7页Chinese Journal of New Drugs

基　　金：上海中医药大学开放基金(S30303)

摘　　要：目的:研究一种新型青蒿素二聚体衍生物SM1052的体外、动物体内抗肿瘤活性及其作用机制。方法:采用体外培养的人子宫内膜癌(RL95-2)细胞株,以CCK-8法测定SM1052对RL95-2细胞增殖的影响;体内实验采用人子宫内膜癌细胞裸鼠移植瘤模型观察SM1052对RL95-2的生长抑制作用;流式细胞检定法(FCM)测定细胞周期的变化;AnnexinⅤ-FITC/PI双染法检测SM1052对RL95-2细胞早期凋亡率的影响;Western blotting测定Bcl-2,Bax蛋白表达变化。结果:SM1052能显著抑制RL95-2细胞增殖,50μmol·L-1细胞存活率为(13.83±0.43)%;SM1052(10 mg·kg-1)对荷瘤裸鼠肿瘤生长有明显抑制作用;SM1052(50μmol·L-1)能诱导细胞引发G2/M期阻滞;能诱导细胞发生凋亡,且以早期凋亡为主;能显著上调Bax、下调Bcl-2蛋白的表达。结论:SM1052在体外、动物体内具有较高的抗人子宫内膜癌(RL95-2)的活性,其作用机制可能通过诱导细胞周期阻滞和调节凋亡蛋白Bcl-2,Bax表达水平相关。Objective： To evaluate the antitumor activity of SM1052, a novel artemisinin derivatives, in the human endometrial carcinoma RL95-2 cells in vitro and in vivo and to investigate the mechanism of action. Methods： Cytotoxic activity of SM1052 in vitro was evaluated by CCK-8 assay in RL95-2 cells. In vivo antitumor activity was tested in nude mice with xenograft of the cancer cells. Cell cycle was determined by flow cytometry, the rate of early apoptosis was measured by flow eytometry using Annexin V-FITC/PI double staining, and the expression of Bcl-2 and Bax proteins was detected by Western blotting. Results： SM1052 significantly inhibited the prolif- eration of RL95-2 cells, and cell viability was （ 13.83 ＋ 0.43 ） % at 50 μmol·L^-1 of SM1052. SM1052 （ 10 mg·kg^-1 ） remarkably inhibited growth of RL95-2 xenografi tumor. SM1052 （50 μmol·L^-1） significantly induced cell cycle arrest in GJM and early apoptosis, increased Bax expression and down-regulated Bcl-2 expression. Conclusion： SM1052 has effective antitumor activity in the human endometrial carcinoma RL95-2 cells in vitro and in vivo. The mechanisms of action may involve induction of cell cycle arrest and regulation of the expression of apoptosis-related proteins （Bcl-2 and Bax）.

关 键 词：青蒿素 双分子衍生物 抗肿瘤 细胞周期 细胞凋亡 

分 类 号：R965.1[医药卫生—药理学] R966[医药卫生—药学]