【摘要】 目的 基于缺氧诱导因子-1α(HIF-1α)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路，探讨丹皮酚对人子宫内膜癌Ishikawa细胞增殖、迁移及侵袭的抑制作用及其机制。方法 体外培养Ishikawa细胞，通过CCK-8实验筛选丹皮酚的最优浓度和干预时间。实验设3组：对照组采用含0.1%DMSO的培养基培养，丹皮酚组采用含50μmol/L丹皮酚的培养基培养，顺铂组采用含10μmol/L顺铂的培养基培养。培养24 h后，CCK-8法检测细胞活力，计算细胞存活率；乳酸脱氢酶(LDH)释放实验检测细胞毒性，计算LDH释放率；划痕实验和Transwell实验分别检测细胞迁移和侵袭能力，计算细胞迁移率和细胞侵袭率；qPCR法检测细胞中HIF-1α、PI3K、Akt、波形蛋白(Vimentin)mRNA表达情况。结果 丹皮酚组及顺铂组细胞存活率、细胞迁移率、细胞侵袭率和细胞中HIF-1α、PI3K、Akt、Vimentin mRNA相对表达量均明显低于对照组(P均<0.05),丹皮酚组上述各指标与顺铂组比较差异均无统计学意义(P均>0.05);丹皮酚组及顺铂组LDH释放率均明显高于对照组(P均<0.05),但丹皮酚组LDH释放率明显低于顺铂组(P<0.05)。结论 丹皮酚可能通过抑制HIF-1α/PI3K/Akt信号通路及下调Vimentin表达，抑制Ishikawa细胞增殖、迁移及侵袭，其效果与顺铂相当，但细胞毒性较低。更多还原

【Abstract】 Objective It is to explore the inhibitory effects of paeonol(PAE) on proliferation, migration and invasion of human endometrial carcinoma(EC) Ishikawa cells and its underlying mechanisms via hypoxia-inducible factor-1α(HIF-1α)/phosphatidylinositide 3-kinases(PI3K)/protein kinase B(Akt) signaling pathway. Methods Ishikawa cells were cultured in vitro, and the optimal concentration and intervention time of PAE were screened by CCK-8 assay. The cells were divided into 3 groups: the control group was cultured in medium containing 0.1% DMSO, the PAE group was cultured in medium containing 50 μmol/L PAE, and the cisplatin group was cultured in medium containing 10 μmol/L cisplatin. After 24 hours of culture, the cell viability was detected by CCK-8 method, and the cell survival rate was calculated; the cytotoxicity was detected by lactate dehydrogenase(LDH) release assays, and the LDH release rate was calculated; the cell migration and invasion abilities were assessed by scratch test and Transwell test, and the cell migration rates and invasion rates were calculated; the mRNA expressions of HIF-1α, PI3K, Akt, and vimentin in the cells were detected by qPCR. Results The cell survival rate, cell migration rate, cell invasion rate, and relative mRNA expressions of HIF-1α, PI3K, Akt and vimentin in the cells of the PAE group and cisplatin group were significantly lower than those in the control group(all P<0.05), but there were no statistically significant differences in the above indicators between the PAE group and cisplatin group(all P>0.05). The LDH release rates of the PAE group and cisplatin group were significantly higher than that of the control group(both P<0.05), and the LDH release rate of the PAE group was significantly lower than that of the cisplatin group(P<0.05). Conclusion PAE can inhibit the proliferation, migration and invasion of Ishikawa cells via inhibiting HIF-1α/PI3K/Akt signaling pathway and down-regulating expression of Vimentin. Its effect is comparable to that of cisplatin, but with lower cytotoxicity.更多还原