Experimental study of HIFU incomplete ablation on the damage effect and prognosis of rabbit VX2 breast cancer model

Abstract

Purpose: High-intensity focused ultrasound (HIFU) represents an emerging noninvasive modality for tumor treatment. While biological responses and immunological change associated with incomplete ablation have not been thoroughly investigated. This study aims to evaluate the damage effect of HIFU incomplete ablation via establishing animal model and further explore its possible mechanism to inhibit tumor growth. Methods: The rabbit VX2 breast cancer model was established and received HIFU treatment with complete ablation (100% tumor volume) and incomplete ablation (about 80% tumor volume) under real-time B-ultrasound monitoring. Histopathological alterations, dynamics of tumor cell apoptosis and proliferation, expression levels of VEGF, MMP-9, IL-2R, TGF-β1, HSP-70, IL-6, IL-8, and INF-γ, and the presence of circulating tumor cells (CTCs) were evaluated post-HIFU incomplete ablation. Results: For HIFU 80% ablation group, there was an 85.85% reduction in tumor volume 21 days post-intervention. A marked increase in tumor cell apoptosis and a concomitant decrease in proliferation were observed. Notably, distant tumor metastasis rates, CTC counts, and expression levels of VEGF, MMP-9, IL-2R, TGF-β1, IL-6, and IL-8 were significantly reduced. In contrast, INF-γ and HSP-70 expressions were notably elevated, aligning with findings from the 100% ablation group. Conclusions: HIFU incomplete ablation, with an 80% tumor ablation rate, induces substantial tumor damage, augments tumor cell apoptosis, and triggers an anti-tumor immune response, curtailing metastasis. These insights may underpin further investigations into the therapeutic implications of HIFU incomplete ablation.