HB-EGF And Chemosensitivity In Ovarian Cancer Cells

Objective: To investigate the effect of CRM197, an HB-EGF inhibitor, on the drugresistance of A2780、A2780/Taxol and A2780/CDDP treated with CRM197.Methods: The expression levels of HB-EGF and EGFR were examined byimmunofluorescence double staining. The mRNA expression of the ATP-bindingcassette subfamily B member1(ABCB1/MDR1), excision repaircross-complementation group1(ERCC1) were analyzed in the parental A2780cellsand resistant cells with and without CRM197using real-time RT-PCR. The expressionlevels of MDR1and ERCC1protein were analyzed using western blotting.Results: The results revealed that CRM197markedly suppressed the expression ofHB-EGF and EGFR. The inhibition of HB-EGF by CRM197significantlydown-regulated the expression of MDR1, P-glycoprotein and ERCC1, which arechemoresistance-related targets with respect to paclitaxel and cisplatin therapies inovarian cancer.Conclusion: CRM197may contribute to revesing the chemoresistance of resistanthuman ovarian cancer cells to paclitaxel and cisplatin therapies, which may be causedby the decreased expression of HB-EGF and EGFR due to the down-regulation ofMDR1and ERCC1.