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目的:通过Janus激酶(JAK)抑制剂AG490在卵巢上皮癌SKOV3细胞中对Survivin基因表达的影响,探讨Survivin基因对肿瘤细胞增殖、凋亡的作用机制,了解Survivin在卵巢上皮癌发展中的作用。方法:不同浓度的AG490作用于SKOV3后,流式细胞仪检测细胞凋亡及细胞周期变化的情况,并以免疫组化法检测STAT3、p-STAT3与Survivin的表达。结果:流式细胞术发现,AG490使SKOV3细胞周期阻滞于G2/M期,S期和G0/G1期细胞数减少,细胞凋亡率明显增加;加用AG490后24h出现凋亡峰,40μmol/L药物处理组凋亡率可达33%,与对照组比较有显著性差异(P<0.05)。免疫组化提示AG490通过抑制JAK酶的活性抑制了STAT3的活化,其活化形式p-STAT3表达率由58.95%下降为20.67%,降低了Survivin的表达,表达率由56.91%下降为16.24%,差异有统计学意义(P<0.05)。结论:在SKOV3中,AG490通过抑制JAK酶的活性,阻断STAT3的活化,进而降低了其下游凋亡抑制蛋白Survivin的表达,促进肿瘤细胞凋亡,抑制肿瘤细胞的异常增殖,表明Survivin可能是卵巢上皮癌的癌基因。
OBJECTIVE: To investigate the effect of Survivin gene on the proliferation and apoptosis of tumor cells and the role of Survivin in the development of epithelial ovarian carcinoma by Janus kinase (JAK) inhibitor AG490 on the expression of Survivin in ovarian epithelial carcinoma SKOV3 cells. Methods: After different concentrations of AG490 were treated with SKOV3, the apoptosis and cell cycle changes were detected by flow cytometry. The expressions of STAT3, p-STAT3 and Survivin were detected by immunohistochemistry. Results: Flow cytometry showed that cell cycle arrest of SKOV3 in G2 / M phase was inhibited by AG490, while the number of cells in S phase and G0 / G1 phase decreased and apoptosis rate increased obviously. / L drug treatment group apoptosis rate up to 33%, compared with the control group had significant difference (P <0.05). Immunohistochemistry showed that AG490 inhibited the activation of STAT3 by inhibiting the activity of JAK enzyme. The expression of p-STAT3 in activated form decreased from 58.95% to 20.67%, and decreased the expression of Survivin, from 56.91% to 16.24% There was statistical significance (P <0.05). CONCLUSIONS: In SKOV3, AG490 can inhibit the activation of STAT3 by inhibiting the activity of JAK enzyme, which in turn reduces the expression of Survivin, which is a downstream inhibitor of apoptosis, promotes the apoptosis of tumor cells and inhibits the abnormal proliferation of tumor cells, indicating that Survivin may be Ovarian epithelial cancer oncogene.