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.


CONCLUSIONS
COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.
Department of Oncology, the Fist Affiliated Hospital of Anhui Medical University, Hefei, China. gukangsheng@yeah.net
Kang-Sheng
KS
Gu
Yu
Y
Chen
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D016328:NF-kappa B; D009578:Nitrobenzenes; D013449:Sulfonamides; D013859:Thiocarbamates; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C066229:prolinedithiocarbamate; D011392:Proline; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D017239:Paclitaxel