Regulation of PPAR? on the growth of pancreatic carcinoma is partly dependent on NF-?B and AP-1 / 中国病理生理杂志

ABSTRACT

AIM: To examine the effects of PPAR? activation on the growth of human pancreatic carcinoma in vitro and to explore the role of NF-?B and activator protein-1 (AP-1) in this process. METHODS: SW-1990 pancreatic cancer cells were treated with ligand of RXR?, 9-cis-RA, ligand of PPAR?, 15d-PGJ_2, and both. Antiproliferative effect was evaluated by using MTT assay; the expression of NF-?B p65 active protein was assayed by using TransAM~TM technique. Expression of c-jun and c-fos by SW1990 cells, which were treated with 15d-PGJ_2, 9-cis-RA and both at varying concentrations, were detected by RT-PCR. RESULTS: MTT assay demonstrated that 15d-PGJ_2, 9-cis-RA and the combination of both had a potent inhibitory effect on the growth of SW1990 cells in a dose-dependent manner. 9-cis-RA had a synergic action with 15d-PGJ_2 on the growth inhibition of pancreatic carcinoma. TransAM~TM showed a down-regulation trend of P65 active protein in SW1990 cells treated with 15d-PGJ_2, 9-cis-RA and both. RT-PCR demonstrated that the expression of c-jun mRNA in 15d-PGJ_2, 9-cis-RA and the combination of both-treated cells were firstly increased and then decreased, the expression of c-fos was decreased in 15d-PGJ_2 or 9-cis-RA treated SW1990 cells, but increased in cells treated with both 15d-PGJ_2 and 9-cis-RA. CONCLUSION: Activation of PPAR? exerts a negative regulatory effect on the growth of pancreatic carcinoma in vitro. Activation of RXR? has a synergic action with PPAR? agonist. The mechanism is probably associated with down-regulating the expression of NF-?B and AP-1. [