Insufficient Radiofrequency Ablation Promotes Epithelial-mesenchymal Transition Mediated by Interleukin-6/signal Transducer and Activator of Transcription 3/Snail Pathway in the H22 Cells

Context: Radiofrequency ablation (RFA), an established and minimally invasive therapy for hepatocellular carcinoma, has become an important treatment strategy. However, tumor aggressiveness remains a common problem. The epithelial-mesenchymal transition (EMT) is thought to play an important role in this process.

Design And Aims: Due to limited sample volumes harvested from patients, we established a heat-treated cell line and a mouse model to investigate the mechanisms of incomplete ablation in EMT.

Materials And Methods: We heat-treated H22 and HepG2 cells using a water bath to determine a suitable temperature for incomplete RFA. Male BALB/c mice were orthotopically transplanted with H22 cells and then subjected to incomplete ablation. Changes in the EMT biomarkers were detected by real-time polymerase chain reaction, western blotting, and immunofluorescence.

Statistical Analysis: The experimental results are expressed as means ± standard deviations.

Results: Incomplete RFA promoted EMT, downregulated E-cadherin, upregulated vimentin and Snail, and enhanced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) both in vivo and in vitro. Moreover, interleukin (IL)-6 secretion increased after heat treatment in the H22 cells. AG490, an IL-6 inhibitor, inhibited the occurrence of EMT.

Conclusions: Insufficient ablation performed at low temperature successfully induces EMT and promotes tumor aggressiveness, which is mediated by the IL-6/STAT3/Snail pathway in both cell and mouse models.