三氧化二砷诱导卵巢癌细胞株COC1发生G_1期阻滞

目的研究三氧化二砷(As2O3)诱导卵巢癌细胞株COC1凋亡的作用机理。方法用不同浓度的As2O3溶液作用人卵巢癌细胞株COC1,于不同时间点收集细胞,MTT法检测细胞生长抑制率,原位末端标记法(TUNEL)观察细胞凋亡形态学特征,流式细胞仪检测细胞凋亡率及分析细胞周期的变化。结果随着药物浓度的升高、作用时间的延长,As2O3对COC1细胞的生长抑制率逐渐升高,具有浓度和时间依赖性;COC1细胞在1.5μmol/LAs2O3作用48h就出现了凋亡形态学改变,且随着作用时间的延长凋亡细胞数量增多;在3.0μmol/L、1.5μmol/LAs2O3作用下COC1出现了明显的凋亡峰,细胞周期也出现了随着药物作用时间的延长G1期细胞比例逐渐上升,S期、G2/M期细胞的比例同时降低的现象,提示As2O3对人卵巢癌细胞株COC1有明显周期特异性生长抑制作用。结论As2O3可以诱导卵巢癌细胞株COC1发生凋亡,诱导细胞发生G1期阻滞是As2O3抑制卵巢癌细胞生长作用的可能机制之一。

Induction of apoptosis of ovarian carcinoma cell strains with As2O3 via G1 phase cell cycle arrest

Objective To study the apoptosis of ovarian carcinoma cell strain COC1 induced by arsenic trioxide (As_2O_3). Methods The effect of arsenic trioxide on the proliferation of ovarian carcinoma cell strains were examined, using Methyl thiazolyl tetrazolium(MTT) assay. Flow cytometry(FCM) was used to detect apoptosis percentage and phase distribution of cell cycles. After being exposed to As_2O_3 solution of different concentration, apoptosis morphologic features of COC1 were observed by TdT-mediated dUTP nick end labeling (TUNEL). Results Inhibition of As_2O_3 on the growth of COC1 was increasing with passing of time and increasing of concentration. After 48h of exposure to 1.5 μmol/L As_2O_3, COC1 cell strains presented apoptosis morphologic change, and the number of apoptosis cells increased with the passage of time. After treatment with 3.0 μmol/L or 1.5 μmol/L As_2O_3, the percentage of COC1 cells in G_2/M phase declined, and the percentage of cells in G_1 phase increased with the passage of time. These results suggested that As_2O_3 inhibited the cellular proliferation of COC1 cells via arrest of cell cycle. Conclusion Arsenic trioxide can induce apoptosis of ovarian carcinoma cell strain COC1. It can block the cell cycle at the G_1 phase, which is one of the possible mechanisms of apoptosis induced by As_2O_3.