Abstract Despite considerable advances, the treatment of pancreatic cancer (PC) still requires much effort. Unusual regulation of the Wnt and apoptotic signaling pathways is widespread in cancer incidence. For instance, the WIF1 (Wnt inhibitory factor 1) gene is down-regulated in many cancers. The purpose of this study was to determine the effects of recombinant Betatrophin, a recently discovered hormone, on MiaPaca-II and Panc-1 pancreatic cell lines. Various concentrations of Betatrophin were added to MiaPaca-II and Panc-1 pancreatic cell lines during periods of 24 , 48, and 72 h. The MTT assay was applied to investigate cell proliferation after treatment. The rate of apoptotic cells was assessed using double-staining flow cytometry, and the expression levels of the WIF1 gene and Bcl2 protein was observed by real-time PCR and western blotting, respectively. The findings of this study suggest that Betatrophin has an anti-proliferative effect on both MiaPaca-II and Panc-1 cell lines, in line with the up-regulation of WIF1 as a tumor suppressor gene. Moreover, the induction of apoptosis by ANGPTL8 occurred by the down-regulation of Bcl2. Thus, Betatrophin can be proposed as a potential therapeutic drug for treating pancreatic cancer.

中文翻译：

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对胰腺癌细胞系的抗增殖和凋亡作用表明 ANGPTL8（Betatrophin）的新作用

摘要 尽管取得了长足的进步，胰腺癌 (PC) 的治疗仍然需要付出很多努力。Wnt 和凋亡信号通路的异常调节在癌症发病率中很普遍。例如，WIF1（Wnt 抑制因子 1）基因在许多癌症中被下调。本研究的目的是确定重组 Betatrophin（一种最近发现的激素）对 MiaPaca-II 和 Panc-1 胰腺细胞系的影响。在 24、48 和 72 小时的时间段内，将不同浓度的 Betatrophin 添加到 MiaPaca-II 和 Panc-1 胰腺细胞系中。MTT测定用于研究处理后的细胞增殖。采用双染流式细胞仪检测细胞凋亡率，实时荧光定量 PCR 和蛋白质印迹法观察 WIF1 基因和 Bcl2 蛋白的表达水平，分别。这项研究的结果表明 Betatrophin 对 MiaPaca-II 和 Panc-1 细胞系都具有抗增殖作用，这与 WIF1 作为肿瘤抑制基因的上调一致。此外，ANGPTL8 诱导细胞凋亡是通过 Bcl2 的下调而发生的。因此，Betatrophin 可以被认为是治疗胰腺癌的潜在治疗药物。