title: Combinational treatment with retinoic acid derivatives in non-small cell lung carcinoma in vitro.
abstract: The growth inhibitory effects of four retinoic acid (RA) derivatives, 9-cis RA, 13-cis RA, N-(4-hydroxyphenyl) retinamide (4-HPR), and all-trans retinoic acid (ATRA) were compared. In addition, the effects of various combinations of these four agents were examined on non-small cell lung carcinoma (NSCLC) cell-lines, and on the expressions of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) on these cells. At the clinically achievable concentration of 1 microM, only 4-HPR inhibited the growths of H1299 and H460 cells-lines. However, retinoic acid receptor beta(RAR beta) expression was up-regulated on H460 and H1299 cells treated with 1 microM of ATRA, 13-cis RA, or 9-cis RA. All NSCLC cell lines showed growth inhibition when exposed sequentially to 1 microM ATRA and 0.1 microM 4-HPR. In particular, sequential treatment with 1 microM ATRA or 13-cis RA and 4-HPR markedly inhibited H1703 cell growth; these cells exhibited no basal RAR beta expression and were refractory to 4-HPR. However, in NSCLC cell lines that expressed RAR beta, the expressional levels of RAR beta were up-regulated by ATRA alone and by sequential treatment with ATRA and 4-HPR. 4-HPR was found to be the most active of the four agents in terms of NSCLC growth-inhibition. Moreover, sequential treatments with ATRA or 13-cis RA followed by 4-HPR were found to have synergistic growth-inhibitory effects and to regulate RAR expression.
authors.affiliation: Department of Internal Medicine and Brain Korea 21 Program for Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Choi
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Whang
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000077556:Alitretinoin; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004359:Drug Therapy, Combination; D017313:Fenretinide / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D047488:Retinoid X Receptors / Q000235:genetics; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D017931:DNA Primers; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; C082925:retinoic acid receptor beta; D017313:Fenretinide; D000077556:Alitretinoin; D014212:Tretinoin; D015474:Isotretinoin