HBOC alleviated tumour hypoxia during radiotherapy more intensely in large solid tumours than regular ones

Abstract

Radiotherapy (RT) is a highly valuable method in cancer therapy, but its therapeutic efficacy is limited by its side effects and tumour radiation resistance. The resistance is mainly induced by hypoxia in the tumour microenvironment (TME). As a nano-oxygen carrier, Haemoglobin-based oxygen carriers (HBOCs) administration is a promising strategy to alleviate tumour hypoxia which may remodel TME to ameliorate radiation resistance and enable RT more effective. In this study, we administered fractionated RT combined with HBOC to treat Miapaca-2 cell and Hela cell xenografts on nude mice. The study found that HBOC relieved hypoxic environment and down-regulate expression of hypoxia-inducible factor-1α (Hif-1α) both in regular (100 mm³) and large (360/400 mm³) tumours. The proliferation and metastasis of tumour tissue also decreased after HBOC application. Nevertheless, in vivo RT combined with HBOC performed more effectively to suppress tumour growth in large tumours than in regular tumours. This is due to more severe hypoxic regions exist in the large solid tumours compared to the regular counterparts, and HBOC administration may be more effective in alleviating hypoxia in large tumours. Thus, HBOC sensitization therapy is more suitable for large solid tumours.

Keywords:

• Haemoglobin-based oxygen carriers (HBOCs)
• tumor hypoxia
• radiotherapy
• xenograft
• Hif-1α

Acknowledgements

The HBOC production used in this study was provided by Redpharm (Beijing) Biotechnology Co. Ltd. We would like to thank Chengmin Yang for contributing towards the administrative aspects of this manuscript, and for his support in general throughout this process.

Author contributions

Yingcan Xu: conceptualization, methodology, investigation, formal analysis, writing-original draft. Kehui Zhu: conceptualization, investigation, data curation. Jiakang Wu and Shifan Zheng: resources, investigation. Rui Zhong: conceptualization, writing—review and editing. Wentao Zhou: supervision, data curation. Ye Cao: conceptualization, writing—review and editing. Jiaxin Liu: conceptualization, supervision, and funding acquisition. Hong Wang: conceptualization and supervision. All authors have agreed to be accountable for all aspects of the work and the submitted version of the manuscript.

Data availability statement

The data supporting the findings of this study are available within the article and its Supplementary Materials.

Additional information

Funding

This work was supported by Sichuan Provincial Department of Science and Technology under Grant No. 2021YJ0122, Sichuan Cancer Hospital under Grant No. 2020FSZLX-05, and CAMS Innovation Fund for Medical Sciences (CIFMS) under Grant No. 2021-I2M-1-060.