三白脂素-8抑制缺氧诱导因子-1α对肾癌细胞能量代谢的影响

Effect of Man A on energy metabolism of renal carcinoma cells when HIF-1α inhibited

目的观察三白脂素-8(Man A)抑制缺氧诱导因子1α(HIF-1α)后对肾癌细胞的生长及能量代谢是否有显著影响,该影响是否与Man A调控了细胞的能量代谢相关。方法构建高表达HIF-1α的肾癌细胞模型,使用不同浓度Man A干预转染后的肾癌细胞(转染组)和单纯肾癌细胞(非转染组)。MTT法检测各组细胞增殖情况;RT-PCR检测细胞内HIF-1α的基因表达;分光光度计检测细胞内ATP水平、丙酮酸含量及SDH活性。结果给予Man A进行干预两种细胞株后HIF-1α的基因表达出现显著下调(P<0.05)。随着干预剂量的增加,细胞内ATP、丙酮酸含量及SDH活性逐渐降低,均在高剂量组出现显著下降(P<0.05)。干预后肾癌细胞的生长增殖受到抑制,中、高剂量组下降显著(P<0.05)。结论 Man A可显著抑制肾癌细胞增殖,降低代表糖酵解及氧化磷酸化的丙酮酸含量及SDH活性水平,并造成ATP生成减少。Man A对能量代谢的影响可能参与了Man A对肾癌细胞的抑制作用。

Objective To observe whether significant inhibitory effect on proliferation and energy metabolism of renal carcinoma cells,when HIF-1α inhibited by Man A,and to explore the possible mechanisms. Methods After successfully constructed the HIF-1α highly expressing cell models,different concentrations of Man A solutions were added to the culture medium,then,proliferation of cells,expressions of HIF-1α. Levels of ATP,pyruvate and SDH were detected by Fluorescence Spectrophotometer. Results HIF-1α expressions were decreased significantly in all of the groups of transferred groups（ P〈0. 05）. Man A can significantly inhibit proliferation of renal carcinoma cells,contents of pyruvate and levels of SDH in the high dosage groups（ P〈0. 05）. While,all the changes were intensified with amount of Man A decreases gradually.Conclusion Man A can significantly inhibit proliferation of renal carcinoma cells,and reduce contents of pyruvate and levels of SDH. Influence on energy metabolism of Man A may participate in the mechanism.