川芎嗪对胃癌细胞增殖、迁移、侵袭及糖酵解的调控作用  

Regulatory effect of tetramethylpyrazine on cell proliferation,migration,invasion,and glycolysis in gastric cancer cells

作　　者：王韩英 陈勇[1] 朱双媚 Han-Ying Wang;Yong Chen;Shuang-Mei Zhu(Department of Tumor Chemoradiotherapy,Lishui People’s Hospital,Lishui 323000,Zhejiang Province,China)

机构地区：[1]丽水市人民医院肿瘤放化疗科,浙江省丽水市323000

出　　处：《世界华人消化杂志》2023年第12期485-491,共7页World Chinese Journal of Digestology

摘　　要：背景川芎嗪(tetramethylpyrazine,TMP)被报道具有抗肿瘤作用,但其对胃癌的作用及其机制并不完全清楚.目的探讨TMP对胃癌细胞增殖、迁移、侵袭和葡萄糖代谢的影响及潜在的作用机制.方法体外培养的胃癌细胞随机分为4组:对照组(control,Ctrl)、低剂量TMP组(TMP-L,10μM)、中剂量TMP组(TMP-M,20μM)、高剂量TMP组(TMP-H,40μM).胃癌细胞经相应处理后,采用CCK-8检测细胞活力、集落形成实验及transwell细胞实验分别用来检测细胞的增殖及迁移侵袭能力;此外,检测细胞的葡萄糖摄取、乳酸生成、氧消耗速率(oxygen consumption rate,OCR)以及胞外酸化率(extra-cellular acidification rate,ECAR)来反映细胞的葡萄糖代谢情况并分析糖酵解关键酶[己糖激酶(hexokinase,HK)和乳酸脱氢酶(lactate dehydrogenase,LDH)]的活性;Western blot检测糖酵解相关蛋白的表达以及蛋白激酶B(protein kinase B,AKT)/葡萄糖转运蛋白1(glucose transporter-1,GLUT1)信号通路的活性.结果TMP可剂量依赖性抑制胃癌细胞的活力(P<0.05).相较于对照组,中、高剂量TMP可抑制细胞增殖、迁移及侵袭(P<0.05).此外,给予TMP干预后,胃癌细胞中葡萄糖摄取量和乳酸产量降低(P<0.05),OCR及ECAR也显著降低(P<0.05);高剂量的TMP可显著降低细胞HK和LDH的活性(P<0.05).Western blot检测结果显示,TMP干预后细胞内p-AKT/AKT、GLUT1、HK2以及LDHA蛋白表达水平均显著下调(P<0.05).结论TMP可降低胃癌细胞的糖酵解水平,抑制细胞的增殖、迁移及侵袭.BACKGROUND Tetramethylpyrazine(TMP)has been reported to have antitumor effects,but its effect on gastric cancer and the underlying mechanism are not fully understood.AIM To investigate the regulatory effect and potential mechanism of TMP on the proliferation,migration,invasion,and glycolysis of gastric cancer cells.METHODS Gastric cancer cells cultured in vitro were randomly divided into four groups:Control group(Ctrl),low-dose TMP group(TMP-L,10μM),medium-dose TMP group(TMP-M,20μM),and high-dose TMP group(TMP-H,40μM).After treatment,cell viability was detected by CCK-8 assay,and cell proliferation,migration,and invasion were detected by colony formation assay and transwell assay.Glucose metabolism was determined by measurements of glucose uptake,lactate production,oxygen consumption rate(OCR),and extracellular acidification rate(ECAR).The activity of hexokinase(HK)and lactate dehydrogenase(LDH)was determined.The expression of glycolysis-related proteins and activation of the protein kinase B(AKT)/glucose trans-porter-1(GLUT1)axis were assessed by Western blot assay.RESULTS TMP reduced the viability of gastric cancer cells in a dose-dependent manner(P<0.05).Compared to the Ctrl group,medium-and high-dose TMP inhibited cell proliferation,migration,and invasion(P<0.05).After treatment with TMP,glucose uptake,lactate production,OCR,and ECAR were decreased significantly(P<0.05),and the activity of HK and LDH was reduced significantly in the TMP-H group(P<0.05).Western blot analysis showed that the expression of p-AKT/AKT,GLUT1,HK2,and LDHA in gastric cancer cells treated with TMP was downregulated(P<0.05).CONCLUSION TMP reduces glycolysis and inhibits cell proliferation and migration in gartric cancer cells.

关 键 词：川芎嗪 胃癌细胞 增殖 迁移 糖酵解 

分 类 号：R285[医药卫生—中药学]