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.