Downregulation of peroxiredoxin I by a novel fully human phage display recombinant antibody induces apoptosis and enhances radiation sensitization in A549 lung carcinoma cells.

Abstract

BACKGROUND:

Antibodies have been proved to be effective in cancer treatment. Peroxiredoxin I (Prx I) is a potential target for cancer radiotherapy. The aim of this article is to investigate the effect of a novel phage display single-chain variable fragment (scFv) antibody targeting Prx I on human lung carcinoma cell line A549 radiosensitivity and the underlying mechanisms.

MATERIALS AND METHODS:

A549 cell radiosensitivity was measured by colony-forming assay; cell cycle, cell apoptosis, and intracellular reactive oxygen species (ROS) level were determined by flow cytometer; RAD51 and γ-H2AX expression was evaluated by Western blot; and caspase 3 expression was determined by immunocytochemistry. A nude mouse bearing A549 tumor was established, and radiation sensitivity was measured to verify the in vitro data.

RESULTS:

Prx I scFv incubation significantly increased A549 cell radiosensitivity, and this might be through enhanced intracellular ROS level and caspase 3 expression. In addition, protein expression of radiosensitivity-related proteins, RAD51 and γ-H2AX, was also modulated. The nude mouse xenograft model bearing A549 tumor treated with Prx I scFv also exibited enhanced radiosensitivity compared with the PBS group.

CONCLUSIONS:

These results suggested that Prx I scFv could become a new therapy candidate for lung cancer radiotherapy.

• Authors: Qishuai Guo, Xi Huang, Jun Zhang, Yi Luo, Zhiping Peng, Shaolin Li
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 27 Issue 5 Pg. 307-16 (Jun 2012) ISSN: 1557-8852 [Electronic] United States
• PMID: 22022930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Fragments
• Peptide Library
• Radiation-Sensitizing Agents
• Peroxiredoxins

Topics

• Animals
• Apoptosis (immunology, radiation effects)
• Cell Line, Tumor
• Combined Modality Therapy
• Down-Regulation
• Female
• Humans
• Immunoglobulin Fragments (immunology, pharmacology)
• Immunohistochemistry
• Lung Neoplasms (genetics, metabolism, radiotherapy, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Peptide Library
• Peroxiredoxins (antagonists & inhibitors, genetics, immunology, metabolism)
• Radiation-Sensitizing Agents (pharmacology)
• Xenograft Model Antitumor Assays