The multi-targeted tyrosine kinase inhibitor vandetanib plays a bifunctional role in non-small cell lung cancer cells.

ABSTRACT: Vandetanib, a multikinase inhibitor, is a target of drug treatments for non-small cell lung cancer (NSCLC). However, phase II and III clinical trials have not conclusively demonstrated the curative effects of vandetanib for NSCLC, and the reasons for this are unknown. In the present study, we use the NSCLC cell line Calu-6 as a model to determine the cellular and biological effects of vandetanib. Our results demonstrate that vandetanib impairs Calu-6 cell migration and invasion. We find that vandetanib can directly inhibit RET activity, which influences the Rho-JNK pathway. Overexpression of a constitutively active Rho GTPase antagonizes the inhibitory effects of vandetanib on Calu-6 cells invasion and JNK pathway activation. In addition, vandetanib induces autophagy by increasing the leve

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC4342569 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature