Pachymic acid suppresses proliferation and invasion in colon cancer by inhibiting glycolysis via PPARγ/ENO1 pathway.

Aerobic glycolysis constitutes a fundamental aspect of the process of tumor development. Pachymic acid, a major active ingredient in Poria cocos, has been reported to impair glucose metabolism in several cancers. However, whether pachymic acid could inhibit the aerobic glycolysis of colon cancer remains to be elucidated. Our study revealed that the treatment of pachymic acid significantly inhibited the proliferation and invasion of HT-29 and HCT-116 cells. Moreover, it led to a substantial reduction in the expression level of glycolysis-related proteins including phosphoglycerate kinase 1 (PGK1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and α-enolase (ENO1). Potential targets of pachymic acid were screened by network pharmacology analysis and molecular docking, and PPARγ was determined as the primary target of pachymic acid according to Western blot and real-time qPCR. Further experiments indicated that the overexpression of PPARγ reversed the inhibitory effects of pachymic acid on the proliferation, invasion and aerobic glycolysis of HT-29 and HCT-116 cells. The inhibition of PPARγ led to a significant reduction in the expression of PGK1, GLUT1, LDHA and ENO1. Subcutaneous tumor-bearing experiments in nude mice verified the antitumor effect of pachymic acid on colon cancer, which could be reversed by the overexpression of PPARγ. The present study confirmed that pachymic acid played an inhibitory role in the proliferation and invasion of colon cancer by intervening in the process of glycolysis. PPARγ was identified as the primary target of pachymic acid in regulating the glucose metabolism in colon cancer.