Mechanism of P-glycoprotein expression in the SGC7901 human gastric adenocarcinoma cell line induced by cyclooxygenase-2.

OBJECTIVE To investigate possible signal pathway involvement in multi-drug resistant P-glycoprotein (P-gp) expression induced by cyclooxygenase-2 (COX-2) in a human gastric adenocarcinoma cell line stimulated with pacliaxel (TAX). METHODS The effects of TAX on SGC7901 cell growth with different doses was assessed by MTT assay, along with the effects of the COX-2 selective inhibitor NS-398 and the nuclear factor-KB (NF-KB) pathway inhibitor pyrrolidine dithiocarbamate (PDTC). Influence on COX-2, NF-KB p65 and P-gp expression was determined by Western blotting. RESULTS TAX, NS-398 and PDTC all reduced SGC7901 growth, with dose- dependence. With increasing dose of TAX, the expression of COX-2, p65 and P-gp showed rising trends, this being reversed by NS-398. PDTC also caused decrease in expression of p65 and P-gp over time. CONCLUSION COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.