汉黄芩素对人胃癌细胞SGC-7901和人脐静脉内皮细胞ECV304增殖抑制及能量代谢的影响  

Effect of Wogonin on Proliferation Inhibition and Energy Metabolism of SGC-7901 Cells and ECV304 Cells

作　　者：王淑静[1] 李岳婷 袁天宇 訾庆雪 张文君[1] 付玉 张家宁[1] WANG Shujing;LI Yueting;YUAN Tianyu;ZI Qingxue;ZHANG Wenjun;FU Yu;ZHANG Jianing(College of Pharmacy,Harbin University of Commerce,Harbin 150076 Heilongjiang,China)

机构地区：[1]哈尔滨商业大学药学院

出　　处：《中药新药与临床药理》2019年第12期1428-1433,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：哈尔滨商业大学科研项目专项基金（17XN073）

摘　　要：目的探讨汉黄芩素(Wogonin)对人胃癌细胞SGC-7901和人脐静脉内皮细胞ECV304增殖抑制及能量代谢的影响及机制。方法采用MTT法和生长曲线法检测汉黄芩素对2种细胞的增殖抑制活性;HE染色法观察细胞形态变化;检测己糖激酶(HK)、丙酮酸激酶(PK)、乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)的活力及三磷酸腺苷(ATP)含量;Western Blot法检测低氧诱导因子-1α(HIF-1α)和单羧基转运体4(MCT4)蛋白表达水平。结果15μg·mL-1汉黄芩素对SGC-7901、ECV304的细胞增殖抑制率较好,且作用相近(P>0.05),故选择该浓度作为后续实验浓度。与对照组比较,汉黄芩素对2种细胞均有明显的持续增殖抑制作用,实验组细胞浓度在第6天下降最为明显(P<0.01);汉黄芩素干预后2种细胞均出现数量变少、胞质凝集等形态变化,SGC-7901细胞改变更为明显;SGC-7901汉黄芩素组的LDH、SDH活力及ATP含量显著降低(P<0.05,P<0.01),ECV304汉黄芩素组的HK活力及ATP含量显著下降(P<0.01);SGC-7901、ECV304细胞在汉黄芩素干预后HIF-1α及MCT4蛋白表达均明显降低(P<0.05,P<0.01)。结论汉黄芩素可能通过下调SGC-7901、ECV304细胞的HIF-1α及MCT4表达,抑制2种细胞不同能量代谢酶活力,减少ATP生成,改善细胞酸性微环境,抑制胃癌细胞增殖和肿瘤血管生成,其对不同细胞能量代谢的影响具有差异性。Objective To investigate the effect and mechanism of Wogonin on proliferation inhibition and energy metabolism of human gastric cancer cells SGC-7901 and human umbilical vein endothelial cells ECV304.Methods MTT assay and growth curve assay were used to detect the inhibitory activities of wogonin on the proliferation of two kinds of cells.Morphological changes of the cells were observed by HE staining.The activities of hexokinase(HK),pyruvate kinase(PK),lactate dehydrogenase(LDH),succinate dehydrogenase(SDH),and ATP content were detected by spectroscopic kit.The expression levels of hypoxia-inducible factor 1 alpha(HIF-1α)and monocarboxylate transporter 4(MCT4)were detected by Western Blot.Results A dose of 15μg·mL-1 Wogonin had good inhibition rates on cell proliferation of SGC-7901 and ECV304,and the effects were similar(P>0.05);and this concentration was selected as the concentration in the follow-up experiments.Compared with the control group,Wogonin had significant inhibitory effect on the continuous proliferation of both kinds of cells,and the densities of cells in the Wogonin groups decreased most significantly on day 6(P<0.05).After the intervention of Wogonin,both cell lines showed morphological changes such as fewer number and cytoplasmic agglutination,and the changes of SGC-7901 cells were more obvious.LDH,SDH activity and ATP content significantly decreased in SGC-7901 Wogonin group(P<0.05,P<0.01);while HK activity and ATP content significantly decreased in ECV304 Wogonin group(P<0.01).The expression of HIF-1αand MCT4 in SGC-7901 and ECV304 cells were significantly decreased after the intervention of Wogonin(P<0.05,P<0.01).Conclusion Wogonin may inhibit enzyme activity in energy metabolism of the two cells by reducing expression of HIF-1αand MCT4 in SGC-7901 and ECV304 cells,reducing ATP production,improving acidic microenvironment of cells,and inhibiting proliferation and tumor angiogenesis of gastric cancer cells,which has different effects on energy metabolism of different cells.

关 键 词：汉黄芩素 人胃癌细胞SGC-7901 人脐静脉内皮细胞ECV304 能量代谢酶 ATP 

分 类 号：R285.5[医药卫生—中药学]