Maehle L, Eilertsen E, Mollerup S, Schønberg S, Krokan H E, Haugen A
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Br J Cancer. 1995 Apr;71(4):691-6. doi: 10.1038/bjc.1995.136.
Several studies have shown that dietary lipid exerts an effect on carcinogenesis. We report here that progression to malignancy in vitro is associated with changes in the response to fatty acids (FAs). Tumorigenic (THKE) cells were more sensitive to the n-3 FAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than immortalised (IHKE) cells. The growth of THKE cells was inhibited 25% more than the growth of IHKE cells at 80 microM EPA (P < 0.01) and 35% more at 40 microM DHA (P < 0.001). Furthermore, the results indicate that there is a wide cell type variation in the response to FAs. We found that the in vitro inhibition by FAs correlated with the reduction in the growth rate of the tumour in nude mice fed K85 (55% EPA and 30% DHA). A significant difference in tumour latency was observed for the A427 cell tumour groups (10 days, P < 0.05). Tumours in the animals fed n-3 FA exhibited significantly higher levels of EPA and DHA; the level of arachidonic acid (ARA) was significantly lower in THKE tumours and the level of linoleic acid (LA) was significantly lower in A427 tumours than in controls fed corn oil. The higher sensitivity of the A427 cell line was not explained by higher uptake of EPA/DHA.
多项研究表明,膳食脂质对致癌作用有影响。我们在此报告,体外恶性进展与对脂肪酸(FAs)反应的变化有关。致瘤性(THKE)细胞比永生化(IHKE)细胞对n-3脂肪酸二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)更敏感。在80微摩尔EPA时,THKE细胞的生长受到的抑制比IHKE细胞多25%(P<0.01),在40微摩尔DHA时多35%(P<0.001)。此外,结果表明,对脂肪酸的反应存在广泛的细胞类型差异。我们发现,脂肪酸的体外抑制作用与喂食K85(55% EPA和30% DHA)的裸鼠肿瘤生长速率的降低相关。A427细胞肿瘤组的肿瘤潜伏期存在显著差异(10天,P<0.05)。喂食n-3脂肪酸的动物体内肿瘤的EPA和DHA水平显著更高;THKE肿瘤中的花生四烯酸(ARA)水平显著低于对照组,A427肿瘤中的亚油酸(LA)水平显著低于喂食玉米油的对照组。A427细胞系较高的敏感性并非由更高的EPA/DHA摄取所解释。