School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong, P.R. China.
Int J Oncol. 2010 Apr;36(4):991-8. doi: 10.3892/ijo_00000579.
Given the reported side effects associated with chemotherapy and surgical resection, dietary intervention with omega-3 polyunsaturated fatty acids (PUFAs) has been postulated to be an alterative way to prevent liver cancer progression and metastasis. We studied the effects of an omega-3 PUFA, docahexaenoic acid (DHA) on COX-2 expression and the cell cycle control machinery that co-ordinately regulate the HCC cells growth. Our data showed that DHA (0-200 microM) retarded proliferation of the human metastatic HCC cell line MHCC97L dose-dependently. In addition, inhibition of cyclin A/Cdk2 interfered with S-phase progression further in agreement with the result of bivariate flow cytometric analysis which indicated that DNA synthesis time (Ts) was significantly prolonged by DHA in MHCC97L. The N-myc oncogene, the heat shock proteins Hsp27 and glucose-related protein 78 (GRP78) as well as the antioxidant enzymes superoxide dismutase may play significant roles in the cell cycle control and reduced-proliferation of MHCC97L by DHA. Our data indicated that it is imperative to develop therapeutic strategy with omega-3 PUFA that simultaneously targets COX-2 and other cell cycle regulators in hepatocarcinogenesis. This study provides novel mechanistic insights into the modulation of DHA on human hepatocarcinoma.
鉴于化疗和手术切除相关的副作用，人们推测，用欧米伽-3 多不饱和脂肪酸（PUFA）进行饮食干预是一种替代方法，可以防止肝癌进展和转移。我们研究了一种欧米伽-3 PUFA，二十二碳六烯酸（DHA）对 COX-2 表达和共同调节 HCC 细胞生长的细胞周期调控机制的影响。我们的数据表明，DHA（0-200 μM）剂量依赖性地延缓了人转移性肝癌细胞系 MHCC97L 的增殖。此外，抑制周期蛋白 A/Cdk2 进一步与双变量流式细胞术分析的结果一致，表明 DHA 显著延长了 MHCC97L 的 S 期进展，从而进一步干扰了 S 期进展。N-myc 癌基因、热休克蛋白 Hsp27 和葡萄糖相关蛋白 78（GRP78）以及抗氧化酶超氧化物歧化酶可能在 MHCC97L 的细胞周期调控和增殖减少中发挥重要作用。我们的数据表明，开发一种用欧米伽-3 PUFA 靶向 COX-2 和肝癌发生过程中其他细胞周期调节剂的治疗策略是至关重要的。本研究为 DHA 对人肝癌的调节提供了新的机制见解。
