胰岛素促进胰腺癌细胞SW1990吸收钠离子机制的研究

Mechanism of insulin promoting absorption of sodium by pancreatic cancer cell SW 1990

目的为解释新发糖尿病合并胰腺癌预后差的现象,本研究拟探讨胰岛素影响胰腺癌细胞钠代谢的分子机制。方法在高糖DMEM中培养胰腺癌细胞SW1990,用不同浓度胰岛素刺激细胞,在不同时间检测培养上清中Na+浓度,分析Na+随胰岛素浓度和时间变化的规律。同时检测胰岛素对血清和糖皮质激素诱导的蛋白激酶1(SGK1)的影响,并分析其中的信号通路。结果胰岛素刺激SW1990细胞后,培养上清中Na+浓度下降(P<0.05),SGK1蛋白表达量增加(P<0.05),且Na+浓度的下降幅度与SGK1蛋白水平相关(r=0.715,P<0.01);胰岛素处理后乙酰化修饰关键基因CREBBP和EP300表达明显上调(P<0.05)。结论胰岛素可促进胰腺癌细胞吸收钠离子,与SGK1基因的表达水平相关,其中乙酰化修饰可能发挥一定作用。

Objective To explain the poor prognosis of new-onset diabetes complicating pancreatic cancer, the impact of insulin on the absorption of sodium by the pancreatic cancer cell （SW1990） was detected. Methods The SW1990 cell line cuhured in the high glucose DMEM medium was stimulated with insulin of gradient concentration, and the concentrations of Na＋ in medium were detected at different time to explore the dose effect and time effect. The impact of insulin on serum and glucocorticoid-inducible kinase 1 （SGK1）, and the possible signaling pathways were also studied. Results The expression of SGK1 was remarkably increased（P〈0.05） while the concentration of Na＋ in cell cuhure solution decreased（P〈0.05） after SW1990 was treated with insulin, and the descending range of Na＋ was positively related to the SGK1 protein level（r=0.715, P=0.009）; the expression of CREBBP and EP300 was closely associated with acetylation elevated apparently after insulin was added（P〈0.05）. Conclusion Insulin can promote the absorption of sodium by the pancreatic cell line, which correlates to the transcription level of SGK1 gene, and acetylation may play a role in this process.