Sb. Jakowlew et al., Retinoic acid down-regulates VPAC(1) receptors and TGF-beta 3 but upregulates TGF-beta 2 in lung cancer cells, PEPTIDES, 21(12), 2000, pp. 1831-1837
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.