Abstract
Purpose
This study aimed to investigate the therapeutic potential of tumor suppression and mechanism for different implantation modes of iodine-125 (I-125) seeds irradiation in a mice xenograft model, and its skeletal complications.
Materials and methods
A total of 24 mice carrying A549 lung tumor-derived xenografts were randomly assigned to four groups, including non-radioactive (sham) seeds implantation, I-125 seeds fractional implantation, I-125 seeds single implantation and I-125 seeds single implantation combined with anlotinib. Ki67 immunohistochemistry, TUNEL immunofluorescence and CD31 morphometric analysis were used to determine the proliferation index, rate of apoptotic cells and microvessel density, respectively. Additionally, the side effects on the skeletal system in mice treated with I-125 seeds implantation were evaluated by histomorphometric staining with tartrate-resistant acid phosphate (TRAP) and alkaline phosphatase (ALP) expression in femur, tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen type I N-terminal propeptide (PINP) levels in serum were evaluated by enzyme-linked immunosorbent assay (ELISA).
Results
The I-125 seeds single and fractionated implantation had similar therapeutic effects and complications when the total number of I-125 seeds was the same. A single implantation of I-125 seeds with or without anlotinib could analogously inhibit the tumor growth in xenografts mice, while the single implantation combined with anlotinib had more effective in tumor inhibition. The results of Ki67, TUNEL and CD31 staining confirmed an evident reduction in tumor cell proliferation and angiogenesis, as well as an increase in apoptosis. A relatively integrated bone metabolism was indicated after I-125 seeds single implantation with or without anlotinib, and the results were similar in I-125 seeds fractional implantation, including a reduction in the number of TRAP-positive cells and an increase in ALP expression level. Additionally, the serum TRACP-5b activity was decreased and the serum PINP concentration was increased following I-125 seeds implantation.
Conclusions
Single and fractionated implantation pattern of I-125 radioactive seeds had similar therapeutic efficacy against tumor growth, while brachytherapy with I-125 seeds implantation may be an effective and safe treatment strategy for its potential protection against cancer treatment-induced bone loss.
Ethics approval and consent to participate
All the animal experimental procedures were approved by the Committee for Ethical Use of Experimental Animal at Fudan University.
Authors contributions
F. H., Q. B., J. B., J. W., and W. G. performed the experiments. F. H., Q. Y., C. W., K. Z., and J. Z. supervised data collection and analysis. F. H., W. S., and G. Z. designed the study and wrote the paper. All authors have read and approved the final version of the manuscript.
Disclosure statement
The authors declare no conflict of interest exits in this manuscript.
Data availability statement
The datasets generated and analyzed in the present study are available from the corresponding author on reasonable request.
Additional information
Funding
Notes on contributors
Feilong He
Feilong He, MSc, graduated from Institute of Radiation Medicine, Fudan University. Now he is a public health physician in Shanghai municipal center for disease control & prevention, Shanghai, PR China.
Qi Bao
Qi Bao, PhD, a professor and associate chief physician of Department of Thoracic Surgery, Long Hua Hospital Affiliated to Shanghai TCM University. His research focuses on effects of traditional Chinese medicine.
Jiangtao Bai
Jiangtao Bai, MSc, MA, a graduated student of Institute of Radiation Medicine, Fudan University, Shanghai, PR China. Her research focuses on effects of bone damage induced by radiation.
Jianping Wang
Jianping Wang, a senior technologist in the Institute of Radiation Medicine, Fudan University, Shanghai, PR China. He has an extent experience in cell culture and animal experiment.
Jianglong Zhai
Jianglong Zhai, MSc, an Assistant Researcher in the Institute of Radiation Medicine, Fudan University, Shanghai, PR China. He has an extent experience in radiotherapy planning.
Qiquan Yu
Qiquan Yu, MSc, MA, an attending physician of Department of Thoracic Surgery, Long Hua Hospital Affiliated to Shanghai TCM University.
Wentao Guo
Wentao Guo, MSc, an attending physician in the Department of Thoracic Surgery, Long Hua Hospital Affiliated to Shanghai TCM University.
Chunxiao Wu
Chunxiao Wu, MSc, an attending physician in the Department of Thoracic Surgery, Long Hua Hospital Affiliated to Shanghai TCM University.
Kun Zhang
Kun Zhang, MSc, an attending physician in the Department of Thoracic Surgery, Long Hua Hospital Affiliated to Shanghai TCM University.
Weizhen Shou
Weizhen Shou, MD, PhD, a Professor and chief physician of Department of Thoracic Surgery, Long Hua Hospital Affiliated to Shanghai TCM University. Dr. Shou’s research focuses on traditional Chinese medicine clinical research.
Guoying Zhu
Guoying Zhu, MD, PhD, a Professor of Radiation Medicine, and a Senior Researcher in the Institute of Radiation Medicine, Fudan University, Shanghai, PR China. Dr. Zhu’s research focuses on effects of bone tissue damage induced by radiation and environmental heavy metal.