Resveratrol-mediated apoptosis in renal cell carcinoma via the p53/AMP-activated protein kinase/mammalian target of rapamycin autophagy signaling pathway

摘要

Resveratrol, known as phytoalexin, is a natural compound. Clinical studies have revealed that resveratrol has a variety of effects including anti-inflammatory, antivirus and tumor suppressor activities. It has been reported that it may serve an important role in renal cell carcinoma (RCC) however, the molecular mechanism underlying resveratrol-induced apoptosis in RCC is still unclear. The aim of the present study was to determine whether resveratrol could suppress RCC progression. Analysis of apoptosis demonstrated that resveratrol may act as a RCC suppressor in a dose- and time-dependent manner. In addition, the results of the MTT and cell migration experiments revealed that resveratrol significantly decreased cell viability and migration. In addition, the expression of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) was downregulated by resveratrol, and the expression of pro-apoptosis gene Bcl-2-associated X was upregulated at the mRNA and protein levels. Resveratrol also promoted the expression of p53 and activated phospho-AMP-activated protein kinase (AMPK). The phosphorylation of mammalian target of rapamycin (mTOR) was inhibited and the autophagy-associated genes, light chain 3, autophagy related (ATG)5 and ATG7, were upregulated at the mRNA and protein levels. In conclusion, resveratrol suppressed RCC viability and migration, and promoted RCC apoptosis via the p53/AMPK/mTOR-induced autophagy signaling pathway.