Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro.
10.3346/jkms.2007.22.S.S52
- Author:
Eun Jung CHOI
1
;
Young Mi WHANG
;
Seok Jin KIM
;
Hyun Jin KIM
;
Yeul Hong KIM
Author Information
1. Department of Internal Medicine and Brain Korea 21 Program for Biomedical Sciences, Korea University College of Medicine, Seoul, Korea. yhk0215@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Non-Small-Cell Lung Carcinoma;
Retinoids;
Chemoprevention;
Fenretinide;
Receptors;
Retinoic Acid
- MeSH:
Base Sequence;
Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/metabolism;
Cell Line, Tumor;
DNA Primers/genetics;
Drug Therapy, Combination;
Fenretinide/administration & dosage;
Gene Expression/drug effects;
Humans;
Isotretinoin/administration & dosage;
Lung Neoplasms/*drug therapy/genetics/metabolism;
Receptors, Retinoic Acid/genetics;
Retinoid X Receptors/genetics;
Tretinoin/administration & dosage/*analogs & derivatives
- From:Journal of Korean Medical Science
2007;22(Suppl):S52-S60
- CountryRepublic of Korea
- Language:English
-
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 micrometer, 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 micrometer of ATRA, 13-cis RA, or 9-cis RA. All NSCLC cell lines showed growth inhibition when exposed sequentially to 1 micrometer ATRA and 0.1 micrometer 4-HPR. In particular, sequential treatment with 1 micrometer 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.
