Zhang Li, Wu Xing Zhong
Department of Biochemistry, Shanghai Medical Celloge, Fudan University, Shanghai 200032.
Shi Yan Sheng Wu Xue Bao. 2003 Dec;36(6):421-7.
In this paper, a significantly effect of N-(4-hydrophenyl) retinamide (4-HPR), a derivative of retinoic acid, was observed on inhibition of migration, invasion, cell growth, and induction of apoptosis in hepatoma cells and B16 melanoma cells. The number of migratory hepatoma cells reduced significantly from the control 201 +/- 27.2 to 58 +/- 5.03 after 6-hour incubation with 4-HPR (p < 0.01, n = 4). The number of migratory B16 melanoma cells reduced from the control 302 +/- 30.1 to 254 +/- 25.04 (p < 0.05, n = 4). The invasive ability of these cells was also suppressed by 4-HPR treatment. Cells that penetrated the artificial membrane matrigel decreased from 27 +/- 13.1 to 11.2 +/- 3.3 in hepatoma cells, from 67.5 +/- 10.1 to 24.3 +/- 3.2 in B16 melanoma cells (p < 0.05, n = 3). Furthermore, cell growth was significantly inhibited especially in B16 melanoma cells and 37.11 +/- 0.94% cells were induced to apoptosis after 48-hour induction by 4-HPR, which was significantly higher than those by retinoic acid treatment (p < 0.05). Although the mechanism of 4-HPR effects was not very clear, over expression of CST, which was inhibited by 4-HPR in our previous study, could diminish the apoptosis--inducing effect by 4-HPR. We believe that 4-HPR has a strong inhibitory effect on melanoma and hepatocarcinoma cells and might become a potent therapeutic agent.
本文观察到视黄酸衍生物N-(4-羟苯基)视黄酰胺(4-HPR)对肝癌细胞和B16黑色素瘤细胞的迁移、侵袭、细胞生长具有显著抑制作用，并能诱导细胞凋亡。与4-HPR孵育6小时后，迁移的肝癌细胞数量从对照的201±27.2显著减少至58±5.03(p<0.01，n = 4)。迁移的B16黑色素瘤细胞数量从对照的302±30.1减少至254±25.04(p<0.05，n = 4)。4-HPR处理也抑制了这些细胞的侵袭能力。穿透人工膜基质胶的肝癌细胞从27±13.1减少至11.2±3.3，B16黑色素瘤细胞从67.5±10.1减少至24.3±3.2(p<0.05，n = 3)。此外，细胞生长受到显著抑制，尤其是在B16黑色素瘤细胞中，4-HPR诱导48小时后，37.11±0.94%的细胞被诱导凋亡，这显著高于视黄酸处理组(p<0.05)。虽然4-HPR作用的机制尚不完全清楚，但在我们先前的研究中被4-HPR抑制的CST过表达可减弱4-HPR的凋亡诱导作用。我们认为4-HPR对黑色素瘤和肝癌细胞具有强大的抑制作用，可能成为一种有效的治疗药物。
