Combination of human plasminogen kringle 5 with ionizing radiation significantly enhances the efficacy of antitumor effect.
Antiangiogenic therapy could destroy tumor vasculature and inhibit tumor growth. It might inhibit tumor growth significantly when used as a single treatment modality and its therapeutic benefit may even be greater when used in combination with established treatment modalities such as radiation therapy (RT). In the present report, we investigated the effect of recombinant human plasminogen kringle 5 domain (rhK5) in combination with ionizing radiation on angiogenesis, tumor growth and survival in a murine Lewis lung carcinoma (LLC) tumor model. Combined treatment using rhK5 and radiotherapy displayed obvious suppressive effect on LLC tumor growth as compared with single treatment with either modality (p < 0.05), and resulted in a more additive effect on tumor growth delay in this model. In addition, combined treatment significantly enhanced the survival of mice and no toxic effect, such as weight loss, was observed. The significant antitumor effect of rhK5 plus radiation was associated with a direct suppression effect on early neoangiogenesis and tumor cell apoptosis. Furthermore, the expression of VEGF and HIF-1alpha in tumor tissue correlated well with decreased vessel density. The results suggest that rhK5 significantly enhances the antitumor activity of RT and could be a potent adjuvant therapeutic approach to improve the efficacy of radiotherapy for lung cancer.
The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, People's Republic of China.
Guang-Hui
GH
Jin
Ding-Yuan
DY
Ma
Ning
N
Wu
Faiz M M T
FM
Marikar
Shun-Zi
SZ
Jin
Wei-Wei
WW
Jiang
Yan
Y
Liu
Zi-Chun
ZC
Hua
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000737:chemistry / Q000188:drug therapy* / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D017024:Chemotherapy, Adjuvant; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010446:Peptide Fragments / Q000627:therapeutic use*; D010958:Plasminogen / Q000627:therapeutic use*; D011839:Radiation, Ionizing; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C491499:plasminogen kringle 5; D010958:Plasminogen