Non-thermal plasma with metformin synergistically induces cell death via upregulating AMPK to suppress energy metabolism

Non-thermal plasma (NTP) has a selective killing effect on a variety of cancer cells in vivo and in vitro, and is considered a potential tumor therapy. In this study, we found that metformin, which has shown promising antitumor effects in previous studies, with NTP synergistically increased cell death including apoptosis in colon cancer cell lines via reducing mitochondrial oxidative phosphorylation and intracellular adenosine triphosphate exhausting cellular energy, mediated through activation of AMP-activated protein kinase (AMPK). Reactive oxygen species was revealed to modulate the activation of AMPK after NTP exposure. Considering the safety and wide clinical use of metformin, the combination of metformin and NTP showed great potential in cancer therapy.