曲古抑菌素A对人卵巢癌细胞系A2780细胞周期的影响

Histone Deacetylase Inhibitor Trichostatin A Modulates Cell Cycle in A2780 Human Ovarian Cancer Cell Line

目的研究曲古抑菌素A(TSA)对人卵巢癌细胞系A2780细胞周期的影响及其相关机制。方法通过流式细胞仪检测不同浓度和时间的曲古抑菌素A对A2780细胞周期的影响;RT-PCR法检测不同浓度和时间的曲古抑菌素A对p21WAF/CIPI mRNA表达水平的影响。结果 100nmol/L曲古抑菌素A作用于A2780细胞,随着作用时间的延长,G2/M期细胞增加,S期细胞减少,在36hG2/M期细胞增加达到顶峰,S期细胞减少到最低;12h后p21WAF/CIPI mRNA表达水平开始增高,于24h达到顶峰,48h后出现下降;不同浓度的TSA作用于A2780细胞,从100nmol/L浓度开始G2/M期细胞增加,S期细胞减少,p21WAF/CIPI mRNA的表达水平出现升高,并随着浓度的增加而升高(P<0.05)。结论曲古抑菌素A通过增加p21WAF/CIPI mRNA表达,影响细胞周期素依赖的蛋白激酶的活性,使细胞周期阻滞于G2/M期,抑制A2780细胞增殖。

Objective To analyze the effect and mechanism of trichostatin A（TSA）on cell cycle in human ovarian cancer cells.Methods Human ovarian cancer cell line A2780 cells were cultured in RPMI 1640 supplement.Flow cytometry analysis and RT-PCR were used to examine the distribution of cell cycles and the level of p21WAF/CIPI mRNA.Results TSA induced increase of G2/M cells increased after the treatment of TSA for 36 hours（P 0.05）;the level of p21WAF/CIPI mRNA expression was upregulated after TSA treatment for 12 hours,the highest leve of its expression occurred at 24 hours,the expression level begun to decrease at 48 hours（P 0.05）.TSA simultaneously induced the decrease of S phase cells in a concentration-dependent manne（rP 0.05）.TSA upregulated the expression of p21WAF/CIPI mRNA in a concentration-dependent manner（P 0.05）.Conclusion TSA could block the G2/M phase and inhibits cell proliferation of A2780 cells through upregulating the expression of p21WAF/CIPI mRNA and the activate cyclin-dependent kinase.