High-frequency irreversible electroporation suppresses invasion and metastasis by targeting SIRT1/2 in highly invasive tumor cells: an in vitro study

Sirtuin proteins have key roles in cancer progression and metastases. However, their role in bioelectrical modulation via high-frequency irreversible electroporation (H-FIRE) remains poorly defined. This study aims to investigate the molecular mechanism by which H-FIRE suppresses invasion and metastasis in highly invasive cancer cells (U87 and U2OS) through SIRT1/2 downregulation. We systematically assessed H-FIRE effects on cell proliferation, clonogenicity, invasion, metastasis, apoptosis, mitochondrial morphology, and SIRT1/2 expression. Our results demonstrated that H-FIRE significantly suppressed proliferation, invasion, and metastasis in both two cell lines, concurrently inducing mitochondrial fragmentation and apoptosis. Crucially, H-FIRE markedly downregulated SIRT1/2 expression. Notably, SIRT activators partially reversed H-FIRE-mediated invasion suppression, whereas SIRT inhibitors enhanced inhibitory effect. These results underscore that H-FIRE impedes the invasion and metastasis of highly invasive tumor cells through inhibition of SIRT1/2 expression and induction of mitochondrial apoptosis. Our findings establish SIRT1/2 as critical molecular targets mediating the anti-metastatic effect of H-FIRE and support its potential as an anti-metastatic therapy.