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

低剂量c-Met酪氨酸激酶抑制剂与索拉非尼对人非小细胞肺癌细胞的协同抗肿瘤作用

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作者:Ling Fu, Liang Guo, Yi Zheng, Zhenyu Zhu, Mingyue Zhang, Xiaohua Zhao, Hongxue Cui

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.

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