Department of Biological Sciences, National University of Singapore, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore.
Gen Comp Endocrinol. 2019 Jun 1;277:112-121. doi: 10.1016/j.ygcen.2019.03.018. Epub 2019 Mar 26.
Hepatocellular carcinoma (HCC) shows clear sex disparity with men being more prone to developing HCC and having higher mortality than women. Previous studies have indicated that sex hormones play important roles in HCC initiation and development, but the effects of sex hormones on HCC in clinical trials remain inconsistent. Using zebrafish liver tumor model co-induced by oncogenes Myc and xmrk, we observed similar sex disparity between male and female zebrafish in liver tumor progression and regression; i.e. male Myc/xmrk transgenic zebrafish developed HCC significantly faster and regressed HCC significantly slower than female Myc/xmrk transgenic zebrtafish. To investigate the effects of sex hormones on liver tumor progression and regression, Myc/xmrk fish were treated with either androgen or estrogen, we observed that androgen promoted HCC progression and retarded HCC regression in females, while estrogen attenuated HCC progression and accelerated HCC regression in males. Furthermore, androgen promoted cell proliferation while estrogen inhibited it. Overall, the present study suggested that sex hormones affected liver tumor progression and regression in the Myc/xmrk transgenic zebrafish.
肝细胞癌（HCC）表现出明显的性别差异，男性比女性更容易患上 HCC，死亡率也更高。先前的研究表明，性激素在 HCC 的发生和发展中起重要作用，但性激素对临床试验中 HCC 的影响仍不一致。使用 Myc 和 xmrk 共同诱导的斑马鱼肝肿瘤模型，我们观察到雄性和雌性斑马鱼在肝肿瘤进展和消退方面存在相似的性别差异；即雄性 Myc/xmrk 转基因斑马鱼比雌性 Myc/xmrk 转基因斑马鱼发展 HCC 的速度明显更快，消退 HCC 的速度明显更慢。为了研究性激素对肝肿瘤进展和消退的影响，我们用雄激素或雌激素处理 Myc/xmrk 鱼，我们观察到雄激素促进雌性 HCC 的进展并延缓 HCC 的消退，而雌激素则减弱雄性 HCC 的进展并加速 HCC 的消退。此外，雄激素促进细胞增殖，而雌激素抑制细胞增殖。总的来说，本研究表明，性激素影响 Myc/xmrk 转基因斑马鱼的肝肿瘤进展和消退。
