Drug resistance hinders effectiveness of human ovarian cancer (OC) therapies, such as cisplatin or paclitaxel therapy. Although dacomitinib, a novel anticancer agent is used against multiple types of cancers, such as non-small cell lung cancer, head and neck cancer, few studies report its effectiveness in drug-resistant human OC cells. In the present study, would healing, microplate spectrophotometer analysis, flow cytometry analysis, western blotting and Gene Expression Omnibus (GEO) analysis were used to detect the synergistic effect of dacomitinib and cisplatin in human OC SKOV-3 or OV-4 cells. Co-administration of dacomitinib and cisplatin significantly reduced viability and promoted cell apoptosis of drug resistant OC cells. In addition, dacomitinib increased Cadherin 1 (CDH1) levels and decreased P-glycoprotein (P-GP) levels in cisplatin-resistant OC cells. In addition, GEO analysis demonstrated that dacomitinib inhibited the epidermal growth factor receptor (EGFR) signaling pathway. In summary, dacomitinib improves chemosensitivity of cisplatin in human OC by regulating CDH1 and P-GP protein levels and inhibiting the EGFR signaling pathway.
Keywords: P-glycoprotein; cadherin 1; cisplatin; dacomitinib; drug resistance; epidermal growth factor receptor signaling pathway; human ovarian cancer.
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