Clifford J L, Menter D G, Wang M, Lotan R, Lippman S M
Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1999 Jan 1;59(1):14-8.
Fenretinide (N-[4-hydroxyphenyl]retinamide (4HPR)) is a retinoid analogue with antitumor and chemopreventive activities. The mechanism of action of 4HPR is not fully understood, but it is hypothesized that this compound acts independently of the nuclear retinoid receptor pathway. To test this hypothesis directly, we have analyzed the activity of 4HPR on a panel of F9 embryonal carcinoma cell lines, which includes wild-type and mutant lines that lack expression of retinoic acid receptor gamma, retinoid X receptor alpha, or both. 4HPR (10 microM) treatment resulted in a rapid induction of cell death in F9 cells, which was responsible for their near elimination by 48 h. This effect occurred in the receptor-null cell lines as well. Treatment of the wild-type cells for 4 days with 1 microM 4HPR also resulted in a primitive endodermal differentiated phenotype that is normally seen upon all-trans-retinoic acid treatment and is characterized by the up-regulation of laminin B1 and type IV collagen. This differentiation response did not occur in the receptor-null cells. Therefore, two distinct effects of 4HPR were identified in this system: a rapid induction of cell death and a slower induction of differentiation, which are likely to be receptor independent and dependent, respectively.
芬维A胺（N-[4-羟基苯基]视黄酰胺（4HPR））是一种具有抗肿瘤和化学预防活性的类视黄醇类似物。4HPR的作用机制尚未完全明确，但据推测该化合物的作用独立于核类视黄醇受体途径。为了直接验证这一假设，我们分析了4HPR对一组F9胚胎癌细胞系的活性，这些细胞系包括缺乏维甲酸受体γ、类视黄醇X受体α或两者表达的野生型和突变型细胞系。4HPR（10微摩尔）处理导致F9细胞迅速发生细胞死亡，这使得它们在48小时内几乎被清除。这种效应在无受体细胞系中也会出现。用1微摩尔4HPR处理野生型细胞4天也会导致一种原始内胚层分化表型，这种表型通常在全反式维甲酸处理时出现，其特征是层粘连蛋白B1和IV型胶原上调。这种分化反应在无受体细胞中并未发生。因此，在该系统中确定了4HPR的两种不同效应：细胞死亡的快速诱导和分化的较慢诱导，这可能分别独立于受体和依赖于受体。
