Nilotinib, A Tyrosine Kinase Inhibitor, Suppresses the Cell Growth and Triggers Autophagy in Papillary Thyroid Cancer

Abstract

Background: Papillary Thyroid Carcinoma (PTC) represents the most common thyroid cancer. Until recently, treatment options for PTC patients are limited. Nilotinib is the second-generation tyrosine kinase inhibitor, and has been widely used in the treatment of Chronic Myeloid Leukemia (CML). Objectives: We aimed to explore whether nilotinib is effective for the suppression PTC cancer progression and the underlying mechanisms. Results: In this study, the three human PTC cell lines (KTC-1, BCPAP, and TPC1) were used to verify the effects of nilotinib on cell growth. The half maximal inhibitory concentration (IC50) was calculated according to the growth curve post nilotinib treatment at different concentrations. Cell counting kit-8 and colony formation analysis were used to monitor cell growth after nilotinib treatment. Cell apoptosis and autophagy related proteins and phosphorylation of PI3K/Akt/mTOR were detected by Western blotting analysis. Methods: Nilotinib treatment could effectively inhibit PTC cell growth, which was accompanied by an increase in apoptosis and induction of autophagy. Mechanistically, nilotinib treatment repressed the phosphorylation of the PI3K/Akt/mTOR pathway. Conclusion: Collectively, our results demonstrated that nilotinib may display anti-tumor effect against PTC via inhibiting PI3K/Akt/mTOR pathway and inducing apoptosis and autophagy.