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

ABSTRACT

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.