The retinoid fenretinide inhibits proliferation and downregulates cyclooxygenase-2 gene expression in human colon adenocarcinoma cell lines

被引:21
|
作者
Merritt, G
Aliprandis, ET
Prada, F
Rigas, B
Kashfi, K
机构
[1] Rockefeller Univ, New York, NY 10021 USA
[2] Univ Milan, Milan, Italy
[3] Amer Hlth Fdn, Valhalla, NY USA
[4] CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA
[5] New York Hosp, Queens Med Ctr, New York, NY 10021 USA
关键词
retinoids; cyclooxygenase; colon cancer; prostaglandins; fenretinide;
D O I
10.1016/S0304-3835(00)00714-X
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Fenretinide [N-(4-Hydroxyphenyl)retinamide, 4-HPR] (10(-10)-10(-6) M) treatment of MT-29 human colon cancer cells for 24-72 h significantly inhibited their growth. Using HCT-15 cells, 4-HPR had limited inhibitory effects on cell proliferation over the same concentration range and time period. The inhibitory effects of 4-HPR on cell growth in HT-29 cells were markedly reduced in the presence of exogenously added prostaglandins (PGs), suggesting a possible role for inhibition of PG synthesis as a mechanism for 4-HPR's antiproliferative effects. Inhibition of PGE(2) production was caused by 4-HPR in a concentration-dependent manner and decreased COX-2 but not COX-1 mRNA levels: this is the first indication that 4 HPR selectively inhibits COX-2 gene expression. Our findings suggest a possible mechanism for the chemopreventive and anti-proliferative effects of 4-HPR. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:15 / 23
页数:9
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