Onco, Vol. 4, Pages 77-86: Inhibitory Effects of Metformin for Pancreatic Neuroendocrine Neoplasms: Experimental Study on Mitochondrial Function

Onco, Vol. 4, Pages 77-86: Inhibitory Effects of Metformin for Pancreatic Neuroendocrine Neoplasms: Experimental Study on Mitochondrial Function

Onco doi: 10.3390/onco4020007

Authors: Shogo Maruzen Seiichi Munesue Mitsuyoshi Okazaki Satoshi Takada Shinichi Nakanuma Isamu Makino Linxiang Gong Susumu Kohno Chiaki Takahashi Hidehiro Tajima Yasuhiko Yamamoto Shintaro Yagi

Although pancreatic neuroendocrine neoplasms (panNENs) are much less common and have a better prognosis than exocrine pancreatic cancers, their recurrence rate is not low, even in Grade 1 (World Health Organization classification) panNEN. Recently, there have been several reports that the progression-free survival in patients with unresectable panNEN could be improved by an antidiabetic drug, metformin, with the co-treatment of everolimus or a somatostatin analog. In this study, we aimed to evaluate the effects of metformin on cell metabolism and viability using the panNEN cell line, QGP-1, and RIN-m in culture. We observed an inhibitory effect of metformin on QGP-1 cell proliferation in a dose-dependent manner. Metformin was found to decrease the oxygen consumption rate in QGP-1 and RIN-m cells after metformin 48 h treatment and immediately after exposure. Cell proliferation was suppressed after metformin treatment. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) expression was increased, and cyclin D1 expression was decreased in RIN-m cells 24 h after metformin treatment by Western blotting in a dose-dependent manner. In conclusion, suppressive mitochondrial respiration and AMPK activation by metformin are, thus, suggested to inhibit panNEN cell viability and cell survival.