Kato Taeko, Kolenic Nicole, Pardini Ronald S
Biochemistry, College of Agriculture, Biotechnology and Natural Resources, University of Nevada, Reno, NV 89557, USA.
Nutr Cancer. 2007;58(2):178-87. doi: 10.1080/01635580701328362.
Human colon carcinoma COLO 205, carrying wild type p53, grown subcutaneously in athymic mice was inhibited 80% by a high fat menhaden oil diet containing a mixture of omega-3 fatty acids compared to the low fat corn oil diet containing omega-6 fatty acids. Feeding a high fat diet of golden algae oil containing docosahexaenoic acid (DHA) as the sole long chain omega-3 fatty acid resulted in 93% growth inhibition. Similar findings were previously reported for WiDr colon carcinoma containing mutated p53 (His237). In vitro, 125 muM DHA inhibited COLO 205 growth by 81%, WiDr by 42%, while eicosapentaenoic acid (EPA) marginally inhibited growth of both lines by approximately 30%. DHA inhibited cell proliferation by 41% in WiDr but did not significantly inhibit proliferation in COLO 205. Cell cycle analysis revealed that DHA arrested cell cycle at Resting/Gap 1 (G0/G1 phase) in WiDr and at Gap 2/Mitosis (G2/M) phase in COLO 205. DHA induced apoptosis in COLO 205 but not in WiDr, and EPA did not induce apoptosis in either line. Taken together, these findings suggest DHA is the primary tumor suppressive omega-3 fatty acid in vivo and in vitro and inhibits cancer growth by p53 dependent and independent pathways, while the marginal inhibition by EPA is p53 independent.
携带野生型p53的人结肠癌COLO 205细胞，在无胸腺小鼠皮下生长，与含ω-6脂肪酸的低脂玉米油饮食相比，含ω-3脂肪酸混合物的高脂鲱鱼油饮食可使其生长抑制80%。喂食以二十二碳六烯酸（DHA）作为唯一长链ω-3脂肪酸的高脂金藻油饮食，可导致93%的生长抑制。先前对含突变型p53（His237）的WiDr结肠癌也有类似的研究结果报道。在体外，125μM DHA可使COLO 205细胞生长抑制81%，使WiDr细胞生长抑制42%，而二十碳五烯酸（EPA）对这两种细胞系的生长仅有约30%的轻微抑制作用。DHA可使WiDr细胞的增殖抑制41%，但对COLO 205细胞的增殖无显著抑制作用。细胞周期分析显示，DHA使WiDr细胞的细胞周期停滞在静止/间隙1期（G0/G1期），使COLO 205细胞的细胞周期停滞在间隙2/有丝分裂期（G2/M期）。DHA可诱导COLO 205细胞凋亡，但不诱导WiDr细胞凋亡，EPA对这两种细胞系均不诱导凋亡。综上所述，这些研究结果表明，DHA是体内外主要的具有肿瘤抑制作用的ω-3脂肪酸，可通过p53依赖和非依赖途径抑制癌症生长，而EPA的轻微抑制作用则不依赖于p53。
