p53 status is a major determinant of effects of decreasing peroxiredoxin I expression on tumor growth and response of lung cancer cells to treatment

Miao Fen Chen, Wen Cheng Chen, Chun Te Wu, Paul Yang Lin, Hungyi Shau, Shuen Kuei Liao, Cheng Ta Yang, Kuan Der Lee

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14 Citations (Scopus)

Abstract

Purpose: The potential roles of peroxiredoxin (Prx) I in carcinogenesis and treatment have been explored. Our previous study revealed differences between A549 (functional p53) and H1299 (null p53) Prx I antisense transfectants. The discrepancy might have resulted from the p53 status. In this study, we further investigated the role of Prx I and p53 on lung cancer growth and the response to treatment in vitro and in vivo. Methods: We established stable A549 and H1299 transfectants with Prx I antisense and p53, respectively. We then examined their characteristics in vitro and used nude mice xenografts of these cell lines to compare their capacity for tumor invasion and spontaneous metastasis and their sensitivity to radiotherapy. Results: Increased reactive oxygen species caused by lower Prx I activity induced p53 expression. In lethal stress, the augmentation of reactive oxygen species was partially reversed by blocking p53 in A549 with Prx I antisense. We demonstrated the potential contribution of p53-dependent mechanisms to inhibit lung tumor growth and increase radiosensitization using H1299 transfected with p53 in vitro and in vivo. An increased p53 level attenuated the capacity of the cells for metastasis by decreasing vascular endothelial growth factor and induced radiosensitization by increased apoptosis and cell senescence and by regulating intracellular reactive oxygen species. Conclusion: These results suggest that p53 status has an important role in the tumor-inhibiting and radiosensitizing effects of decreasing Prx I. Both Prx I and p53 may be powerful prognosticators for lung cancer.

Original languageEnglish
Pages (from-to)1461-1472
Number of pages12
JournalInternational Journal of Radiation Oncology Biology Physics
Volume66
Issue number5
DOIs
Publication statusPublished - Dec 1 2006
Externally publishedYes

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Keywords

  • Lung cancer
  • p53
  • Peroxiredoxin I
  • Radiation sensitivity
  • Reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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