A novel role of AIM2 inflammasome-mediated pyroptosis in radiofrequency ablation of hepatocellular carcinoma

Abstract

Abstract Background Hepatic inflammation and inflammasome-mediated mechanisms are involved in the pathogenesis of hepatocellular carcinoma (HCC). The absent in melanoma 2 (AIM2) protein triggers activation of the inflammasome cascade. It currently remains unclear whether AIM2 plays a role in HCC and radiofrequency ablation (RFA), which uses radiofrequency waves to treat tumors. This study aimed to investigate whether RFA can induce pyroptosis, also known as cell inflammatory necrosis, in HCC through AIM2-inflammasome signaling in vivo and in vitro. Methods BALB/c nude mice were used to generate HepG2 or SMMC-7721 cell-derived tumor xenografts. HCC cells with knockdown or overexpression of AIM2 were created using short hairpin RNA (shRNA) and expression vector transfection, respectively, for functional and mechanistic studies. Downstream effects were examined using flow cytometry, qRT-PCR, ELISAs, and other molecular assays. Results RFA could significantly suppress tumor growth in mice bearing HCC cell xenografts. Flow cytometry analysis revealed that RFA could induce pyroptosis. Furthermore, AIM2, NLRP3, caspase-1, γ-H2AX, and DNA-PKc had significantly greater expression levels in the liver tissues from mice treated with RFA compared with those of the controls. Additionally, interleukin (IL)-1β and IL-18 expression levels were significantly higher in the HCC cell-derived xenograft mice treated with RFA compared with those without RFA. Notably, a significantly greater effect was achieved in the RFA complete ablation group versus the partial ablation group. Moreover, knockdown or overexpression of AIM2 in HCC cells demonstrated that AIM2 exerted a role in RFA-induced pyroptosis. Conclusions These data indicate that RFA can suppress HCC tumor growth by inducing pyroptosis via AIM2, which serves as an important cell death mechanism. Therefore, therapeutically intervening with AIM2-mediated inflammasome signaling may help improve RFA treatment outcomes for HCC patients.