Retinoic acid down-regulates VPAC1 receptors and TGF-β3 but upregulates TGF-β2 in lung cancer cells

The effects of retinoic acid (RA) on lung cancer cells were investigated. Both all-trans (t-RA) and 13-cis RA (c-RA) decreased specific I-125-VIP binding 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 Scatchard analysis, the density of VIP binding sites but not the affinity was reduced 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 by VIP was reduced by 38% if the NCI-H1299 cells were treated with t-RA. Using the MTT assay, 3 muM t-RA and 3 muM c-RA inhibited NCI-H 1299 proliferation by 60 and 23% respectively. Also, transforming growth factor (TGF)-beta2 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.