Zou Changping, Zhou Jianwei, Qian Linxin, Feugang Jean M, Liu Jia, Wang Xinru, Wu Sheng, Ding Hong, Zou Changchun, Liebert Monica, Grossman H Barton
Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ 85724, USA.
Front Biosci. 2006 Sep 1;11:2007-16. doi: 10.2741/1942.
Clinical trials have explored the use of natural and synthetic retinoids for the prevention of bladder cancer recurrence. Natural retinoids have been shown to inhibit bladder cancer growth. Here, we compared the effects of natural and synthetic retinoids in bladder cancer cells. Bladder cancer cell lines were treated with all-trans-retinoid acid (ATRA), N-4-hydroxyphenyl-retinamide (4-HPR) and 6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid (CD437). Their effects on cell growth, apoptosis, cell cycle, gene expression, and retinoid acid receptors (RARs) and the JWA-retinoid response gene were assessed. Most of the bladder cancer cells were resistant to ATRA (1 and 10 microM). 4-HPR inhibited cell growth by 90% at 10 microM; however, CD437 showed the same effect at 1 microM. 4-HPR and CD437 increased G1 and decreased S phase. The three retinoids differentially affected p53, RARs, and JWA. Only CD437 increased Caspase 3 expression. The results demonstrated that 4-HPR and CD437 were more potent growth inhibitors and apoptosis inducers than ATRA. However, 4-HPR was effective at a concentration at least 10 microM. The in vitro results suggested the higher dose of 4-HPR in chemoprevention trial be considered.
临床试验已探索使用天然和合成类视黄醇预防膀胱癌复发。天然类视黄醇已被证明可抑制膀胱癌生长。在此，我们比较了天然和合成类视黄醇对膀胱癌细胞的影响。膀胱癌细胞系用全反式视黄酸（ATRA）、N - 4 - 羟基苯基视黄酰胺（4 - HPR）和6 - [3 -（1 - 金刚烷基）- 4 - 羟基苯基] - 2 - 萘甲酸（CD437）处理。评估了它们对细胞生长、凋亡、细胞周期、基因表达、视黄酸受体（RARs）和JWA - 视黄酸反应基因的影响。大多数膀胱癌细胞对ATRA（1和10微摩尔）耐药。4 - HPR在10微摩尔时可抑制细胞生长90%；然而，CD437在1微摩尔时就显示出相同效果。4 - HPR和CD437增加G1期并减少S期。这三种类视黄醇对p53、RARs和JWA有不同影响。只有CD437增加半胱天冬酶3表达。结果表明，4 - HPR和CD437比ATRA是更有效的生长抑制剂和凋亡诱导剂。然而，4 - HPR至少在10微摩尔浓度时才有效。体外结果提示在化学预防试验中应考虑使用更高剂量的4 - HPR。
