J Cancer 2020; 11(2):479-487. doi:10.7150/jca.33029 This issue

Research Paper

Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1

Xianbin Zhang1,2✉, Peng Liu3, Yuru Shang2,4, Hagen Kerndl1, Simone Kumstel1, Peng Gong3, Brigitte Vollmar1, Dietmar Zechner1

1. Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059, Rostock, Germany;
2. Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, 250117, Jinan, China;
3. Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055, Shenzhen, China;
4. Molecular Oncology and Immunotherapy, Department of General Surgery, Rostock University Medical Center, Schillingallee 69, 18059, Rostock, Germany.

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Citation:
Zhang X, Liu P, Shang Y, Kerndl H, Kumstel S, Gong P, Vollmar B, Zechner D. Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1. J Cancer 2020; 11(2):479-487. doi:10.7150/jca.33029. Available from https://www.jcancer.org/v11p0479.htm

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Abstract

The poor survival rate of pancreatic cancer is still a major challenge for the clinicians and their patients. In this study, we evaluated the efficacy of metformin, an inhibitor of oxidative phosphorylation, in combination with LW6, which impairs malate dehydrogenase 2 activities, in treating pancreatic cancer cells. We observed that this combinational therapy significantly reduced cell proliferation, migration, and significantly induced cell death when compared to cells treated by each monotherapy or Sham. In addition, we found that the combination of metformin and LW6 increased the phosphorylation of yes-associated protein 1 at serine 127 and attenuated the nuclear localization of this transcription factor. This combinatorial treatment also decreased the level of cellular yes-associated protein 1. This suggests that metformin in combination with LW6 impairs pancreatic cancer cells and reduces nuclear localization of yes-associated protein 1.

Keywords: Metformin, LW6, YAP1