Abstract 248: Eicosapentaenoic acid attenuates obesity-related hepatocellular carcinogenesis

Abstract

Abstract The population of obesity caused by excess energy intake and insufficient physical activity is increasing worldwide. Excess accumulation of body fat is a risk of health, indeed obesity is associated with the pathogenesis of various disease including type II diabetes, cardiovascular disease and cancer. Among various kinds of cancer, the risk of hepatocellular carcinoma (HCC) is strongly influenced by obesity. Studies using diet-induced obesity mouse models show that obesity enhances tumor development inducing chronic inflammation in liver. In fact, obesity failed to promote HCC formation in the absence of inflammatory cytokines IL-6 and TNF-α. Eicosapentaenoic acid (EPA), an omega-3 polysaturated fatty acid, has been shown its anti-inflammatory properties and could be therapeutically useful to ameliorate inflammatory diseases. However, little is known about the effects of EPA on liver cancer which is linked to obesity-related inflammation. Therefore, we tested the effects of EPA on obesity-induced inflammatory response and following tumor development. We used the hepatic procarcinogen dietylnitrosamine (DEN) to induce HCC formation in mice. Since high-fat diet (HFD) can induce obesity and significantly enhance HCC formation in DEN-injected mice, this model is useful to assess tumor promotion on obesity. Using this model, we examined therapeutic potential of EPA in obesity-related cancer. As a result, we found that tumor growth in mice fed HFD supplemented with EPA was reduced compared to HFD-fed mice, indicating that EPA attenuates obesity-related hepatocarcinogenesis. Interestingly, EPA had no obvious effects on obesity-induced inflammation, instead, inhibited tumor growth by suppression of the protumorigenic transcription factor Stat3 signaling. These data suggest translational implications for the treatment of obesity-related HCC. Citation Format: Akane Inoue-Yamauchi, Hiroko Itagaki, Hideaki Oda. Eicosapentaenoic acid attenuates obesity-related hepatocellular carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 248. doi:10.1158/1538-7445.AM2017-248