雷公藤红素对SGC-7901细胞和ECV304细胞增殖及能量代谢的影响  

Effect of celastrol on anti-proliferation and energy metabolism in SGC-7901 cells and ECV304 cells

作　　者：王淑静[1] 董立强[1,2] 刘欢[1] 赵健凯[1] 孙微微[1] 任爽[1] 张寒[1] 

机构地区：[1]哈尔滨商业大学药学院,黑龙江哈尔滨150076 [2]绥化学院食品与制药工程学院,黑龙江绥化152061

出　　处：《中草药》2016年第21期3854-3860,共7页Chinese Traditional and Herbal Drugs

基　　金：研究生创新科研项目(YJSCX2014-338HSD);哈尔滨市科技创新人才研究专项基金(RC2016QN003047)

摘　　要：目的研究雷公藤红素对人胃癌细胞SGC-7901和人脐静脉内皮细胞ECV304增殖抑制活性及能量代谢干预的作用机制。方法选取SGC-7901和ECV304细胞,采用MTT法、生长曲线测定雷公藤红素对2种细胞增殖抑制活性;HE染色法观察细胞形态变化;分光光度法测定糖酵解途径酶[己糖激酶(HK)、丙酮酸激酶(PK)和乳酸脱氢酶(LDH)]、三羧酸循环酶[琥珀酸脱氢酶(SDH)]的活力及能量代谢产物ATP的量;Western blotting法测定低氧诱导因子(HIF-1α)和单羧基转运体(MCF-4)蛋白表达水平。结果雷公藤红素对SGC-7901和ECV304细胞增殖抑制作用具有时间和剂量依赖性,引起2种细胞形态变化,降低2种细胞HK、LDH和SDH活力,使细胞内ATP的量明显减少,SGC-7901细胞中HIF-1α和MCT-4表达明显降低,而ECV304细胞内2种蛋白表达下降不明显。结论雷公藤红素通过降低SGC-7901细胞和ECV304细胞中HIF-1α和MCT-4蛋白表达水平,抑制2种细胞能量代谢相关酶活力,导致能量不足,细胞增殖受到抑制,从而达到抑制胃癌细胞生长和肿瘤血管生成的双重抗肿瘤作用。Objective To investigate the activity of celastrol on the proliferation and the mechanism of energy metabolism to human gastric cancer cells （SGC-7901） and human umbilical vein endothelial cells （ECV304）. Methods SGC-7901 and ECV304 were determined to analyze the proliferation inhibitory rate of celastrol to two kinds of cells by MTT method and growth curve; HE staining method was used to observe the morphological changes; Using spectrophotometric method, the activities of the enzymes in glycolytic pathway （hexokinase, pyruvate kinase, and lactate dehydrogenase） were determined, the enzyme in the tricarboxylic acid cycle （succinate dehydrogenase）, and the level of ATP which was the end-products in energy metabolism were determined; The Western blotting method was used to determine the expression levels ofhypoxia inducible factor （HIF-lα） and single carboxyl transporter （MCF-4）. Results The proliferation inhibition of celastrol to SGC-7901 and ECV304 cells showed in a time- and dose-dependent manner, led to morphologic changes of cells, reduced the activity of ilK, LDH, and SDH, lowered the level of ATP; There was no effect to PK. The protein expression levels of HIF-lα and MCF-4 were significantly reduced. The inhibition ofcelastrol to SGC-7901 was stronger than that of ECV304 cells. Conclusion Celastrol influence energy metabolism of the two cells by reducing the expression levels of HIF-lu and MCF-4 is significant, and then proliferation can be inhibited. It shows a double inhibition on human gastric cancer cells and angiogenesis of tumor.

关 键 词：雷公藤红素 能量代谢 糖酵解 己糖激酶 丙酮酸激酶 乳酸脱氢酶 低氧诱导因子 单羧基转运体 抗肿瘤 

分 类 号：R285.5[医药卫生—中药学]