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.

Keywords:

• HIFU incomplete ablation
• breast cancer
• apoptosis
• anti-tumor immune
• metastasis

Acknowledgments

Thanks to the State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering for providing the experimental platform. Thanks to the members of this research group, advisors and mentors for their help. Thanks to the support of the Chongqing Graduate Research Innovation Project Fund (No. CYS20213).

Authors’ contributions

Xiaoling Feng, Jianhu Li and Hongjian Liao conducted molecular and animal experiments. Min Yang, Zhifei Zhang completed the sequencing data analysis and participated in data. Xiaoling Feng completed the manuscript writing. Qi Wang and Yonghong Du conceived and designed the study, and revised the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.