Retinoic acid down-regulates VPAC(1) receptors and TGF-beta 3 but upregulates TGF-beta 2 in lung cancer cells

The effects of retinoic acid (RA) on lung cancer cells were investigated. B oth all-trans (t-RA) and 13-cis RA (c-RA) decreased specific I-125-VIP bind ing to NCI-H1299 cells in a time- and concentration-dependent manner. After 20 hr, 30 muM t-RA decreased specific I-125-VIP binding by 60%. By Scatcha rd analysis, the density of VIP binding sites but not the affinity was redu ced by 42%. NCI-H1299 VPAC(1) receptor mRNA was reduced by 48%. VIP caused a 3-fold elevation in the NCI-H1299 cAMP, and the increase in cAMP caused b y VIP was reduced by 38% if the NCI-H1299 cells were treated with t-RA. Usi ng the MTT assay, 3 muM t-RA and 3 muM c-RA inhibited NCI-H 1299 proliferat ion by 60 and 23% respectively. Also, transforming growth factor (TGF)-beta 2 increased after treatment of NCI-H1299 cells with t-RA whereas TGF-beta1 mRNA was unaffected and TGF-beta3 mRNA was decreased. These results suggest that RA may inhibit lung cancer growth by down-regulating VPAC(1) receptor and TGF-beta3 mRNA but up-regulating TGF-beta2 mRNA. (C) 2000 Published by Elsevier Science Inc.