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

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.