【摘要】 目的观察乙酰丹参酮ⅡA(ATA)对人卵巢癌细胞增殖和凋亡的诱导作用及对雌激素诱发蛋白TFF1表达的影响,探讨可能的作用机制。方法通过MTT法计算ATA对卵巢癌细胞的活力以及IC50值;用流式细胞术检测凋亡率及细胞周期变化情况;用实时荧光定量聚合酶连反应(RT-PCR)检测TFF1 m RNA的表达水平,并通过构建双荧光素酶报告基因系统分析ATA对TFF1启动子活性的影响。结果 ATA对多种人卵巢癌细胞系均具有增殖抑制作用,对表达雌激素受体ER的肿瘤细胞效果最明显;能使SKOV3细胞周期阻滞在G2/M期,并诱导SKOV3细胞凋亡;能促进TFF1 m RNA的表达;能增强TFF1启动子的转录活性,且在TFF1启动子区域,AP-1结合位点对TFF1启动子的活性起绝对性作用。结论 ATA能有效抑制SKOV3的生长并可促进TFF1启动子的转录活性。更多还原

【Abstract】 OBJECTIVE To observe the cell growth inhibition and apoptotic ability as well as the effect to the expression of TFF1 of acetyltanshinone ⅡA( ATA). METHODS MTT assay was used to check the effect of ATA on the proliferation of ovarian cancer cells and to calculate IC50; Flow cytometry and RT- PCR were respectively used to measure the effect of ATA on SKOV3 cell cycle progression,apoptosis and the expression levels of TFF1 m RNA. Dual- Luciferase Report Gene System was constructed to study the effects of ATA to the activity of TFF1 Promote. RESULTS ATA strongly inhibited the proliferation of all ovarian cancer cells including one breast cancer cells. ER expression was shown to confer resistance to ATA- induced inhibition of proliferation. Flow cytometry analysis indicated that ATA induced cell cycle delay in the G2 / M phase in SKOV3 cells and apoptosis. ATA treatment induced the expression of TFF1 m RNA,an estrogen- induced gene. Mechanistically,ATA increased the activity of TFF1 promoter. Further studies found that,in5’area of TFF1 promoter,only AP- 1 transcription factor binding site plays a key role in the activity of TFF1 promoter,not that of the ERE binding site. CONCLUSION ATA can effectively inhibit the proliferation of SKOV3 cells and promote the activity of TFF1 promoter.更多还原