mTOR/PKM2和STAT3/c-Myc信号通路串话调节胃癌能量代谢和酸性微环境的机制研究

背景:c-Myc和PKM2在多种肿瘤中高表达,但mTOR/PKM2和STAT3/c-Myc信号通路对胃癌调节作用的研究不多见。目的:探讨mTOR/PKM2和STAT3/c-Myc信号通路串话调节胃癌能量代谢和酸性微环境的机制。方法:PKM2和c-Myc慢病毒转染人胃癌AGS和HGC-27细胞,构建敲减PKM2、c-Myc的细胞模型。采用CCK-8法检测细胞增殖能力,Transwell小室法检测细胞迁移能力,流式细胞术检测细胞凋亡,实时定量PCR和蛋白质印迹法分别检测PKM2、c-Myc、LDHA、STAT3、p-STAT3、GLUT-1 mRNA和蛋白表达,比色法检测乳酸和葡萄糖水平。结果:PKM2和c-Myc表达在胃癌细胞中上调。敲减c-Myc可抑制胃癌细胞增殖能力,细胞迁移能力明显降低,LDHA、GLUT-1蛋白表达明显降低,葡萄糖和乳酸含量明显降低。共同敲减PKM2和c-Myc对胃癌细胞增殖能力和糖酵解代谢的抑制作用更明显。mTOR/PKM2与STAT3/c-Myc信号通路之间存在相关性。结论:PKM2联合c-Myc可能成为胃癌新的治疗靶点。

Mechanism of Crosstalk Between mTOR/PKM2 and STAT3/c-Myc Signaling Pathways in Regulating Energy Metabolism and Acidic Microenvironment of Gastric Cancer

Background:Expressions of c-Myc and PKM2 are high in many tumors.However,studies on the regulation of mTOR/PKM2 and STAT3/c-Myc signaling pathways in gastric cancer are rare.Aims:To investigate the mechanism of crosstalk between mTOR/PKM2 and STAT3/c-Myc signaling pathways in regulating energy metabolism and acidic microenvironment of gastric cancer.Methods:Human gastric cancer AGS and HGC-27 cells were transfect with PKM2 and c-Myc lentivirus to construct cell models of knockdown of PKM2,c-Myc.CCK-8 assay was used to detect cell proliferation,cell migration was detected by Transwell chamber,cell apoptosis was determined by flow cytometry.The mRNA and protein expressions of PKM2,c-Myc,LDHA,STAT3,p-STAT3,and GLUT-1 were determined by real-time quantitative PCR and Western blotting,respectively.Lactic acid and glucose levels were detected by colorimetric method.Results:Expressions of PKM2 and c-Myc were up-regulated in gastric cancer.Knockdown of c-Myc could inhibit cell proliferation and migration,decrease protein expressions of LDHA,GLUT-1 and levels of glucose and lactic acid.The inhibition of gastric cancer was more obvious when both PKM2 and c-Myc were knockdown.mTOR/PKM2 signaling pathway was correlated to STAT3/c-Myc signaling pathway.Conclusions:PKM2 combined with c-Myc may be considered as a new therapeutic target for gastric cancer.