Abstract 4147: Synergistic effect of combined EGFR and Src inhibitor in colon cancer cell migration

Abstract

Abstract EGFR signaling plays the important role in cancer cell proliferation and cell migration. Cetuximab which is the antibody against EGFR was approved for colon cancer treatment. Recently, Src inhibitor, dasatinib has been demonstrated to improve drug sensitivity to cetuximab in KRAS mutant colorectal cancer cell growth. Src is a non-receptor tyrosine kinase which is necessary for full activation of EGFR and also functions in focal adhesion kinase activity in cell migration, therefore, the combination of cetuximab and dasatinib may has effect on colon cell migration. In this study, cetuximab and dasatinib were applied to SW480 colon cell which is KRAS mutant cell line. Cell viability and cell migration were analyzed, localization of Src and focal adhesion kinase (FAK) were observed by confocal microscopy. In the result, Combination of 5μM cetuximab and 40 nM dasatinib treatment resulted in synergistic effect on cell viability. However, when cetuximab combined with 25nM dasatinib was applied in trans-well migration assay, the synergistic inhibition on cell migration was observed. The immunofluorescence confocal microscopic image demonstrated cetuximab treatment induced phospho-Src accumulation on the cell membrane and colocalized with phospho-FAK. When the combination of 5μM cetuximab and 25 uM dasatinib were applied in the cell, the membrane accumulation of phospho-Src and Phospho-FAK were decreased. Taken together, cetuximab combined with dasatinib has synergistic efficacy in colon cancer cell proliferation, however, cetuximab combined with lower concentration of dasatinib (25nM) suppressed cell migration by inhibited FAK membrane localization through Src inactivation. Citation Format: Yi-Che Wu, Wan-Chen Wei, Wei-Ting Chao. Synergistic effect of combined EGFR and Src inhibitor in colon cancer cell migration. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4147. doi:10.1158/1538-7445.AM2015-4147