Increase in efficacy of cancer radiotherapy by combination with whole-body low dose irradiation

• Published in: International journal of radiation biology 2008, Vol.84 (3), p.201-210
• Main Authors: Wu, Ning, Jin, Shun-Zi, Pan, Xue-Na, Liu, Shu-Zheng
• Format: Article
• Language: English
• Subjects: Animals; anticancer immunity; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - radiotherapy; Carcinoma, Lewis Lung - secondary; Carcinoma, Lewis Lung - therapy; Cell Line, Tumor; Combined Modality Therapy; Cytotoxicity, Immunologic; Early Growth Response Protein 1 - genetics; gene therapy; Genetic Therapy; Genetic Vectors; Interleukin-18 - genetics; Lewis lung cancer; low dose whole-body irradiation; Lung Neoplasms - immunology; Lung Neoplasms - radiotherapy; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lysosomal Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; radiotherapy; Whole-Body Irradiation
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/09553000801902133

Purpose:Design of cancer radiotherapy protocol to reduce radiation dose and increase treatment efficacy in Lewis lung cancer (LLC) model. Methods: C57BL 6J mice subcutaneously implanted with LLC were treated by conventional radiotherapy (2Gy × 6) combined with LDWBI (low dose whole-body irradiation; the second, third, fifth and sixth local doses of 2Gy each substituted by LDWBI with 0.075Gy) and or gene therapy (intratumor injection of pEgr-IL-18-B7.1 plasmid 24 h before the first and fourth local doses). Immunologic mechanisms were explored. Results: Cancer control was most significantly improved in the group receiving local radiotherapy combined with LDWBI and gene therapy as shown by prolongation of mean survival time by 60.4%, reduction in average tumor weight by 70.8%, decrease in pulmonary metastasis by 66.9% and decrease in intratumor angiogenesis by 64.8% as compared to local radiotherapy alone (p < 0.05). These changes in tumor growth and progression were accompanied with up-regulation of host immunity manifested by stimulated NK (natural killer) and CTL (cytotoxic T lymphocyte) activity, IFN (interferon)-gamma and TNF (tumor necrosis factor)-alpha secretion, PKC (protein kinase C)-theta activation and LAMP (lysosomal associated membrane protein)-1 expression. Conclusion: Combination of conventional radiotherapy with LDWBI and gene transfer could reduce total radiation dose by 2 3 and at the same time improve treatment efficacy of cancer accompanied with up-regulated host anticancer immunity.