Beck S A, Smith K L, Tisdale M J
Cancer Research Campaign Experimental Chemotherapy Group, Aston University, Birmingham, United Kingdom.
Cancer Res. 1991 Nov 15;51(22):6089-93.
The effect of the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) on host body weight loss and tumor growth has been investigated in mice bearing a cachexia-inducing colon adenocarcinoma, the MAC16. EPA effectively inhibited both host weight loss and tumor growth rate in a dose-related manner with optimal effects being observed at a dose level of 1.25 to 2.5 g/kg. At these concentrations host body weight was effectively maintained, and there was a delay in the progression of growth of the tumor, such that overall survival was approximately doubled in EPA-treated animals, using the criteria dictated by the United Kingdom Coordinating Committee for the welfare of animals with neoplasms. Even when tumor growth resumed, weight loss did not occur. Animals bearing the MAC16 tumor showed a decreased protein synthesis and an increased degradation in skeletal muscle. Treatment with EPA significantly reduced protein degradation without an effect on protein synthesis. The effect of GLA on both host body weight loss and tumor growth was much less pronounced than that of EPA, with an effect only being seen at a dose of 5 g/kg, at which some toxicity was observed. In vitro studies showed that while EPA was effective in inhibiting tumor-induced lipolysis, GLA was ineffective in this respect. However, prostaglandin E1, which is formed from GLA in vivo, showed partial reversal of tumor-induced lipolysis and probably accounted for the anticachectic effect of GLA. These results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.
在携带可诱发恶病质的结肠腺癌MAC16的小鼠中，研究了多不饱和脂肪酸二十碳五烯酸（EPA）和γ-亚麻酸（GLA）对宿主体重减轻和肿瘤生长的影响。EPA以剂量相关的方式有效抑制宿主体重减轻和肿瘤生长速率，在1.25至2.5 g/kg的剂量水平观察到最佳效果。在这些浓度下，宿主体重得到有效维持，肿瘤生长进程延迟，因此，根据英国肿瘤动物福利协调委员会规定的标准，经EPA处理的动物总体生存期约延长一倍。即使肿瘤生长恢复，体重也未减轻。携带MAC16肿瘤的动物骨骼肌中蛋白质合成减少，降解增加。EPA处理显著降低蛋白质降解，而对蛋白质合成无影响。GLA对宿主体重减轻和肿瘤生长的影响远不如EPA明显，仅在5 g/kg的剂量下有作用，且在此剂量下观察到一些毒性。体外研究表明，EPA能有效抑制肿瘤诱导的脂肪分解，而GLA在这方面无效。然而，体内由GLA形成的前列腺素E1显示出对肿瘤诱导的脂肪分解有部分逆转作用，这可能是GLA抗恶病质作用的原因。这些结果表明，由于先前的研究表明鱼油的另一种主要成分二十二碳六烯酸在该系统中无药理活性，作为纯脂肪酸的EPA应作为抗恶病质和抗肿瘤药物进行临床研究。
