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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 study the antitumor activity and mechanism of in vivo and in vitro anti-tumor activity of a novel artemisinin dimer derivative SM1052. Methods: The effects of SM1052 on the proliferation of RL95-2 cells were determined by the method of CCK-8 using in vitro cultured human endometrial carcinoma (RL95-2) cell line. The in vivo experiments were performed on human uterine endometrial carcinoma xenografts The effect of SM1052 on the growth of RL95-2 cells was detected by flow cytometry (FCM). The effect of SM1052 on the early apoptosis rate of RL95-2 cells was detected by AnnexinⅤ-FITC / PI double staining. -2, Bax protein expression changes. Results: SM1052 could significantly inhibit the proliferation of RL95-2 cells, the survival rate of 50μmol·L-1 cells was (13.83 ± 0.43)%; SM1052 (10 mg · kg-1) significantly inhibited the growth of tumor-bearing nude mice; SM1052 (50μmol·L-1) could induce G2 / M arrest induced by cell cycle, induce cell apoptosis and mainly induce early apoptosis, up-regulate Bax and down-regulate Bcl-2 protein expression. CONCLUSIONS: SM1052 has high anti-human endometrial carcinoma (RL95-2) activity in vitro and in vivo. The mechanism may be related to the induction of cell cycle arrest and regulation of Bcl-2 and Bax expression.