ROCK inhibitor inhibits the growth and migration of oral squamous cell carcinoma via up-regulated autophagy by suppressing AKT/mTOR pathway

Abstract

Abstract Background Rho-associated protein kinase(ROCK) plays important roles in cell proliferation and migration, depending on cancer types. ROCK inhibitor Y-27632 was referred as a potential immunotherapy strategy for cancer treatment. Oral squamous cell carcinoma (OSCC) remains one of the most aggressive oral carcinoma types. Y-27632 was shown to block the growth, migration and invasion of Cal27 cells, but no detailed studies of underlying mechanisms have been reported. Methods In this study we explored the effect of Y27632 on OSCC (Cal27, SCC4, SCC9) by comparing with and without Y27632 treatment in vitro and in vivo. And further investigations were done to reveal the expression of AKT/mTOR pathway by Biochemical assays, additionally AKT activator (SC79) or mTOR activator (3BDO) was utilized to evaluate the roles of AKT/mTOR pathway in Y27632-induced tumor suppression. Results Our data showed Y-27632 had a strong inhibitory activity against OSCC (Cal27, SCC4, SCC9). In vivo assays confirmed that Y-27632 suppressed OSCC growth by reducing cell proliferation, and importantly Y-27632 did not have any evident toxicity on normal tissues. Biochemical assays demonstrated that Y-27632 inactivated the AKT/mTOR pathway, and treatment with SC79 or 3BDO, respectively AKT and mTOR activator rescued the cell growth and migration inhibition elicited by Y-27632. Further investigations revealed that Y-27632 could enhance cell autophagy by suppressing AKT/mTOR pathway. Conclusions Our study demonstrated that Y-27632 significantly suppressed the AKT/mTOR pathway to promote cell autophagy to inhibit OSCC growth, providing a potential therapeutic drug for OSCC treatment in the future.