Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

Numerous studies have demonstrated that resveratrol has a potential use in cancer prevention and treatment. However, the effects of resveratrol on cancer cell motility and invasiveness remain unclear. The current study aimed to examine the effects of resveratrol on cell migration and invasion in human glioblastoma cells, and to explore the underlying molecular mechanisms. In wound-healing and Matrigel transwell assays, resveratrol was found to significantly inhibit the migration and invasion of U87MG, T98G and U251 glioblastoma cells in vitro. Results from western blot analysis and gelatin zymography revealed that resveratrol also suppressed the expression and activity of matrix metalloproteinase 2 (MMP-2; P<0.05), an important mediator of cell migration and invasion. Furthermore, using a pull-down assay, increased activation of RhoA was observed in glioblastoma cells treated with resveratrol vs. controls (P<0.05). Notably, inhibition of the RhoA/Rho-associated kinase (ROCK) pathway by C3 transferase or Y-27362 was found to attenuate the resveratrol-induced reductions in cell migration and invasion (P<0.05), and also partially rescued the decreased expression and activity of MMP-2 induced by resveratrol (P<0.05). Taken together, the results suggest that resveratrol may inhibit glioblastoma cell motility and invasiveness via activating the RhoA/ROCK signaling pathway.