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

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）.