Pre-treatment with Bifidobacterium infantis and its specific antibodies enhance targeted radiosensitization in a murine model for lung cancer

摘要

Purpose The hypoxic microenvironments of solid tumours are complex and reduce the susceptibility of cancer cells to chemo- and radiotherapy. Conventional radiosensitisers have poor specificity, unsatisfactory therapeutic effects, and significant side effects. Anaerobic bacteria colonise and destroy hypoxic areas of the tumour and consequently enhance the effects of radiation. Methods In this study, we treated a Lewis lung carcinoma transplant mouse model with Bifidobacterium infantis (Bi) combined with its specific monoclonal antibody (mAb) and radiotherapy (RT) to investigate its ability to radiosensitise the tumour. The tumour metabolism and hypoxia in the tumour tissue were monitored by micro-F-18-FDG and F-18-FMISO PET/CT imaging. Immunohistochemistry was used to detect phosphorylated histone (gamma-H2AX), proliferation (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumour necrosis factor-alpha (TNF-alpha), hypoxia-inducible factor-1 alpha (HIF-1 alpha), and glucose transporter 1 (Glut-1) levels. Results Tumour growth was slowed and survival time was markedly prolonged in mice subjected to the combination of B. infantis, specific antibody, and radiotherapy. Levels of HIF-1 alpha, Glut-1, Ki-67, and CD31 expression, as well as uptake of FDG and FMISO, were the lowest in the combination-treated mice. In contrast, gamma-H2AX and TNF-alpha expression levels were elevated and hypoxia in tumour tissue was reduced compared with controls. Conclusion In conclusion, our data indicated that the curative effect of radiotherapy for lung cancer was enhanced by pre-treating mice with a combination of B. infantis and its specific monoclonal antibody.