COX-2 contributes to P-glycoprotein-mediated multidrug resistance via phosphorylation of c-Jun at Ser63/73 in colorectal cancer.

Cross-drug resistance in multidrug-resistant (MDR) cells, which overexpress P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major impediment to successful chemotherapy for colorectal cancer. In the present study, drug-sensitive HCT8 and multidrug-resistant (vincristine, VCR) HCT8/V colorectal cancer cell lines were used to examine the role of c-Jun NH2-Terminal Kinase- (JNK) signaling pathway in P-gp-mediated MDR associated with Cyclo-oxygenase-2 (COX-2). The results showed that SP600125, a JNK inhibitor, and NS-398, a COX-2 inhibitor, significantly reduced the degree of MDR in HCT8/V cells.