Preliminary exploration for effect of EphA2 on drug resistance of colorec-tal carcinoma cells / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of Eph receptor A2 (EphA2) on drug resistance of colorectal carci-noma cells and its possible mechanisms .METHODS:Real-time PCR and Western blot were used to detect the expression of EphA2 at mRNA and protein levels in LoVo and LoVo/5-FU cells.EphA2 siRNA was transfected to down-regulate the EphA2 expression in LoVo/5-FU cells, and the drug sensitivity was calculated by CCK-8 assay.Meanwhile, cell migration and invasion were measured by wound healing assay and Transwell assay , and the protein levels of E-cadherin,β-catenin, N-cadherin, vimentin, Notch and Snail were determined by Western blot .RESULTS: The expression of EphA2 at both mRNA and protein levels was significantly up-regulated in LoVo/5-FU cells (P<0.05).Knockdown of EphA2 suppressed the cell viability, and migration and invasion abilities , but promoted drug sensitivity of LoVo/5-FU cells.Up-regulation of E-cadherin and β-catenin, and down-regulation of N-cadherin and vimentin were observed , indicating that the epithelial-mesenchymal transition ( EMT) process was suppressed .Knockdown of EphA2 decreased the expression levels of Notch and Snail.CONCLUSION:Down-regulation of EphA2 partly reverses drug resistance of LoVo/5-FU cells.The mechanism may be related to suppressing cell growth , migration, invasion and EMT process via Notch/Snail signaling pathway .