title: [Effect of peroxiredoxin I gene silencing on the radiosensitivity of breast carcinoma MCF-7 cell xenograft in nude mice].
abstract: OBJECTIVE
  To investigate the effect of peroxiredoxin I (Prx I) gene silencing on the radiosensitivity of breast carcinoma MCF-7 cell xenograft in nude mice and explore the mechanism.
  
  
  METHODS
  MCF-7 cells were transfected with the recombinant plasmids pGPU6-PrxI and pGPU6-HK separately. The pGPU6-PrxI-transfected cells stably expressing Prx I shRNA and pGPU6-HK-transfected cells were inoculated subcutaneously into BALB/c nude mice. After exposure to ionizing radiation (IR) with 6 MV X-ray, the xenografts were harvested for measuring the tumor volume and mass, and the tumor inhibition rates were calculated. Immunohistochemistry was employed for detecting the expressions of Prx I and caspase-3 proteins. The ultrastructural changes of the tumor tissues following the exposure were observed using electron microscopy. Western blotting was used to analyze the expressions of γ-H2AX and Rad51 proteins.
  
  
  RESULTS
  Following IR exposure, the pGPU6-Prx I-transfected cell xenograft showed a significantly delayed growth and smaller tumor volume as compared with pGPU6-HK xnegraft, with a tumor inhibition rate reaching 79.76%, significantly higher than that in non-exposed pGPU6-Prx I group (34.92%) and pGPU6-HK+IR group (56.94%) (P<0.05). The pGPU6-Prx I-transfected xenografts showed significantly increased tumor cell apoptosis and necrosis, down-regulated the expressions of Prx I and Rad51 proteins, and up-regulated the expressions of caspase-3 and γ-H2AX proteins; these changes were even more obvious after IR exposure, which caused a decrease of Rad51 protein by 84.8% and an increase in γ-H2AX protein by 5.6 folds compared with those in pGPU6-HK group (P<0.05).
  
  
  CONCLUSIONS
  Prx I gene silencing can significantly enhance the radiosensitivity of breast carcinoma xenograft in nude mice possibly by increasing DNA damage and lowering the capacity of the cells for DNA repair. Prx I may serve as an ideal molecular target for radiosensitization of breast carcinoma.
authors.affiliation: Department of Radiation Medicine, Chongqing Medical University, Chongqing 400016, China. guoqis@sohu.com
authors.forename: Qi-shuai
authors.initials: QS
authors.lastname: Guo
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.forename: Shao-lin
authors.initials: SL
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D054464:Peroxiredoxins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D054464:Peroxiredoxins