Anti proliferative and apoptotic effects on pancreatic cancer cell lines indicate new roles for ANGPTL8 (Betatrophin)

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.

Keywords:
Betatrophin; Wnt; WIF1 ; Bcl2 ; pancreatic cancer