Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells.

Abstract

Sorafenib is a multikinase inhibitor that is frequently used to treat various types of malignant tumors. However, it has been demonstrated that Sorafenib only has a moderate antitumor efficacy and is associated with numerous side effects in non-small cell lung cancer (NSCLC), which greatly limits its clinical application. The present study aimed to examine the effects of a combination of Sorafenib and low-dose PF-2341066, a selective c-Met tyrosine kinase inhibitor, on the proliferation, apoptosis and migration of the NSCLC cell line NCI-H1993. The data indicated that treatment with a combination of Sorafenib and low-dose PF-2341066 was able to significantly inhibit the proliferation and migration as well as promote the apoptosis, of NCI-H1993 cells, compared with treatment with Sorafenib or low-dose PF-2341066 alone. Further experiments indicated that the levels of phosphorylated epidermal growth factor receptor and c-Met were significantly decreased following the combined treatment of Sorafenib and PF-2341066, compared with the treatment with Sorafenib or PF-2341066 alone. The findings of the present study indicated that using a low-dose c-Met inhibitor enhances the antitumor activity of Sorafenib in NSCLC and may provide a novel strategy for the treatment of NSCLC.