三氧化二砷诱导卵巢癌细胞株SKOV_3和COC1凋亡

Comparative study on apoptosis of ovarian carcinoma cell line SKOV_3 and COC1 induced by arsenic trioxide

目的:对比研究三氧化二砷(As2O3)诱导卵巢癌细胞株SKOV3和COC1凋亡的作用.方法:用不同浓度的As2O3溶液作用人卵巢癌细胞株SKOV3及COC1,于不同时间点收集细胞,MTT法检测细胞生长抑制率,流式细胞仪检测细胞凋亡率及分析细胞周期的变化,原位末端标记法观察细胞凋亡形态学特征.结果:不同浓度的As2O3溶液对卵巢癌细胞株SKOV3及COC1均有不同程度的生长抑制作用.随着药物浓度的升高、作用时间的延长,As2O3对COC1细胞的生长抑制率升高.15.0μmol/L(10ppc)浓度组的As2O3对SKOV3的生长抑制效应最显著.低于15.0μmol/L的浓度组对SKOV3细胞株的抑制率之间没有显著性差异.As2O3对COC1细胞的生长抑制作用比SKOV3强.6.0μmol/LAs2O3作用48hSKOV3细胞出现凋亡形态学改变,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增多.15.0和6.0μmol/LAs2O3作用下SKOV3细胞周期的变化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.在3.0和1.5μmol/LAs2O3作用下COC1细胞周期也出现了相同的改变.结论:As2O3可以诱导卵巢癌细胞株SKOV3和COC1发生凋亡,COC1比SKOV3对砷剂更敏感.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.

AIM: To compare the apoptosis of ovarian carcinoma cell line SKOV 3 and COC1 induced by arsenic trioxide (As 2O 3). METHODS: The ovarian carcinoma cell lines SKOV 3 and COC1 were induced by As 2O 3 at different concentrations and the cells were harvested at the designated time points. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the growth inhibitory rate of the cells and the flow cytometry (FCM) was used to detect apoptosis percentage and phase distribution of cell cycles. After exposure to different concentrations of As 2O 3 solution, the apoptosis morphologic features of SKOV 3 and COC1 were observed by TdT-mediated-dUTP nick end labeling (TUNEL). RESULTS: The growth of SKOV 3 and COC1 cells was inhibited by different concentrations of As 2O 3 solution. The inhibitory effect increased with time and concentration. 15.0 μmol/L(10 ppc)As 2O 3 had the best inhibitory effect on SKOV 3 cell line while under the dose of 15.0 μmol/L(10 ppc)As 2O 3, no significant difference was found in the inhibition rate of SKOV 3 cell between groups. As 2O 3 had a weaker inhibitory effect on the growth of SKOV 3 cells than on COC1 cells. After 48 h of exposure to 1.5 μmol/L As 2O 3, COC1 cell line presented some morphologic changes of apoptosis. The number of apoptosis cells increased with the time. But the similar results could be observed in SKOV 3 cell line at least after 48 h of exposure to 6.0 μmol/L As 2O 3. After treatment with 15.0 μmol/L or 6.0 μmol/L As 2O 3, the percentage of SKOV 3 cells in G2/M phase declined and the percentage of cells in G1 phase increased with the time. The similar results were observed in COC1 cell line after exposure to 3.0 μmol/L or 1.5 μmol/L As 2O 3. CONCLUSION: As 2O 3 can induce apoptosis in ovarian carcinoma cell lines SKOV 3 and COC1. COC1 cell line is more sensitive to As 2O 3 than SKOV 3 cell line. As 2O 3 can block cell cycle arrest at the G1 phase, which may be one of the mechanisms of apoptosis induced by As 2O 3.