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


CONCLUSIONS
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.
Wu
Ning
N
Immunology Laboratory, MH Radiobiology Research Unit, Jilin University School of Public Health, Changchun, China.
Jin
Shun-Zi
SZ
Pan
Xue-Na
XN
Liu
Shu-Zheng
SZ
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary / Q000628:therapy; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D051766:Early Growth Response Protein 1 / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D020382:Interleukin-18 / Q000235:genetics; D008175:Lung Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014916:Whole-Body Irradiation; D052118:Lysosomal-Associated Membrane Protein 1
D051766:Early Growth Response Protein 1; D020382:Interleukin-18; D051907:Lysosomal Membrane Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1