Juan Yang1,2, ZhouXue Wu1, Yao Chen1,2, ChuanFei Hu1, Dong Li1, Yue Chen2, Saber Imani1, QingLian Wen1, ShaoZhi Fu3,4, JingBo Wu5,6. 1. Department of Oncology, The Affiliated Hospital of Southwest Medical University, #25 Taiping Street, Jiangyang District, Luzhou City, Sichuan Province, 646000, People's Republic of China. 2. Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, People's Republic of China. 3. Department of Oncology, The Affiliated Hospital of Southwest Medical University, #25 Taiping Street, Jiangyang District, Luzhou City, Sichuan Province, 646000, People's Republic of China. shaozhifu513@163.com. 4. Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, People's Republic of China. shaozhifu513@163.com. 5. Department of Oncology, The Affiliated Hospital of Southwest Medical University, #25 Taiping Street, Jiangyang District, Luzhou City, Sichuan Province, 646000, People's Republic of China. wjb6147@163.com. 6. Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, People's Republic of China. wjb6147@163.com.
Abstract
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-18F-FDG and 18F-FMISO PET/CT imaging. Immunohistochemistry was used to detect phosphorylated histone (γ-H2AX), proliferation (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumour necrosis factor-α (TNF-α), hypoxia-inducible factor-1α (HIF-1α), 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-1α, 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, γ-H2AX and TNF-α 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.
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-18F-FDG and 18F-FMISO PET/CT imaging. Immunohistochemistry was used to detect phosphorylated histone (γ-H2AX), proliferation (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumour necrosis factor-α (TNF-α), hypoxia-inducible factor-1α (HIF-1α), 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-1α, 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, γ-H2AX and TNF-α 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.
Authors: Chetan Bettegowda; Long H Dang; Ross Abrams; David L Huso; Larry Dillehay; Ian Cheong; Nishant Agrawal; Scott Borzillary; J Michael McCaffery; E Latice Watson; Kuo-Shyan Lin; Fred Bunz; Kwamena Baidoo; Martin G Pomper; Kenneth W Kinzler; Bert Vogelstein; Shibin Zhou Journal: Proc Natl Acad Sci U S A Date: 2003-12-01 Impact factor: 11.205