Inhibition of lung tumor growth and augmentation of radiosensitivity by decreasing peroxiredoxin I expression.
OBJECTIVE
In this study, we examined the role of peroxiredoxin I (Prx I) in lung cancer cell growth in vitro and in vivo and its influence on these tumor cells' sensitivity to radiotherapy.


METHODS
We established stable transfectants of A549 (p53+) and H1299 (p53-) lung carcinoma cell lines with Prx I antisense to downregulate their Prx I protein. We then examined their in vitro biologic changes and used nude mice xenografts of these cell lines to compare tumor invasion, spontaneous metastatic capacity, and sensitivity to radiotherapy.


RESULTS
The Prx I antisense transfectants of both cell lines showed a significant reduction in Prx I protein production. Prx I antisense transfectants grew more slowly than did the wild type. As xenografts in mice, A549 Prx I antisense transfectants showed a threefold delay in the generation of palpable tumors. The incidence of spontaneous metastasis of Prx I antisense transfectants was significantly less than that of the wild-type cells. Furthermore, irradiation of Prx I antisense transfectants caused more than twice the growth delay compared with the wild type.


CONCLUSIONS
The results of these studies suggest that inactivation of Prx I may be a promising approach to improve the treatment outcome of patients with lung cancer.
Chen
Miao-Fen
MF
Department of Radiation Oncology, Chang Gung Memorial Hospital, and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taipei, Taiwan.
Keng
Peter C
PC
Shau
Hungyi
H
Wu
Chun-Te
CT
Hu
Yueh-Chiang
YC
Liao
Shuen-Kuei
SK
Chen
Wen-Cheng
WC
D000818:Animals; D045744:Cell Line, Tumor; D004249:DNA Damage; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects; D017382:Reactive Oxygen Species; D014162:Transfection; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D010544:Peroxidases; D054464:Peroxiredoxins