关键词: 普罗布考, 代谢重编程, Warburg效应, 侵袭

Abstract:

AIM: To study the mechanism of probucol modulated the metabolic reprogramming of HepG2, reversed the Warburg effect and inhibited its metastasis and invasion, so as to provide support for the research of lipid metabolism regulating drugs. METHODS: HepG2 cells were divided into control group (NC), high dose group (High), middle dose group (Middle) and low dose group (Low) after cultured in vitro. The cells in the high dose, middle dose and low dose group were treated with probucol of 100, 50, 10 μmol/L, respectively. CCK8 was used to detect cell viability; the cell cycle changes were detected by flow cytometry; the cell migration assay was performed by cell scratch test; the cell invasion ability was detected by Transwell experiment; the expression of hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), phospho fructose kinase (PFKP), pyruvate dehydrogenase (PDH) and citric acid synthase (CS) in cells were detected by Western blot; the level of lactic acid in the medium was detected by the kit; the pressure of glycolysis was detected by ECAR; and the oxygen absorption was detected by the 929 oxygen system. RESULTS:Probucol dosedependently inhibited the proliferation of HepG2, and blocked cell cycle. Probucol increased the expression of HK, PK, LDH, PFKP, PDH and CS, increased oxygen consumption and reduced the production of lactic acid, and promoted the cycle of three carboxylic acids. Probucol also inhibited the invasion and migration of HepG2. CONCLUSION: Probucol can regulate the metabolic reprogramming, reverse the Warburg effect of hepatoma cell HepG2，which can inhibit the proliferation, migration and invasion of tumor cells.

Key words: probucol, metabolic reprogramming, Warburg effect, invasion