125I seed irradiation induces apoptosis and inhibits angiogenesis by decreasing HIF-1α and VEGF expression in lung carcinoma xenografts.
The purpose of this study was to examine the effects of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on angiogenesis. A group of 40 mice bearing A549 lung adenocarcinoma xenografts was randomly separated into 4 groups: control group (n=10), sham seed (0 mCi) implant group (n=10), 125I seed (0.6 mCi) implant group (n=10) and 125I seed (0.8 mCi) implant group (n=10), respectively. The body weight and tumor volume, were recorded every four days until the end of the study. At 30 days after irradiation, the microvessel density, proliferative index and apoptotic index were evaluated by quantitative morphometric analysis of the expression of CD34, proliferating cell nuclear antigen (Ki-67) and in situ terminal transferase-mediated fluorescein deoxy- UTP nick-end labeling (TUNEL), respectively. The changes in the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by real-time PCR and western blot analysis. Consequently, 125I seed irradiation suppressed the growth of lung cancer xenografts in nude mice, while inhibiting cell proliferation and angiogenesis and inducing apoptosis as demonstrated by Ki67, CD34 and TUNEL staining. HIF-1α and VEGF mRNA and protein expression levels were substantially downregulated following 125I seed irradiation. Collectively, our data suggest that irradiation by 125I seeds is a promising new option for lung cancer treatment.
Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Gui-Ling
GL
Xiang
Department of International Clinic, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.
Xin-Hong
XH
Zhu
Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Cun-Zhi
CZ
Lin
Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Li-Jun
LJ
Wang
Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Yong
Y
Sun
Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Yi-Wei
YW
Cao
Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Fang-Fang
FF
Wang
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007457:Iodine Radioisotopes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A