title: Adenovirus-mediated transfer of siRNA against peroxiredoxin I enhances the radiosensitivity of human intestinal cancer.
abstract: Peroxiredoxin I (Prx-I), a key member of the peroxiredoxin family, reduces peroxides and equivalents through the thioredoxin system. Our previous work has shown that expression of Prx-I in mammalian cells increases following ionizing radiation (IR), and suppression of its expression enhances radiation-induced cell death in vitro, suggesting that inhibition of Prx-I might be an important pretreatment for cancer radiotherapy. To test this hypothesis in vivo, we suppressed the expression of Prx-I in the human intestinal cancer cell line SW480 by adenovirus-mediated transfer of siRNA. Our results showed that expression of Prx-I in SW480 cells was dramatically reduced by recombinant Ad-SiPrxI, which resulted in decreased cell growth and increased cell death by IR. Significantly more cell apoptosis was detected by flow cytometry analysis when Prx-I expression was knocked down. To evaluate the effect of recombinant Ad-SiPrxI in vivo, xenografts were pretreated with adenovirus before IR. Tumor growth in mice was inhibited when the xenografts were pretreated with Ad-SiPrxI before IR. Our results suggest that pretreatment with recombinant adenovirus to inhibit Prx-I expression can enhance the radiosensitivity of cancer cells, and thus might be a potential application in clinical therapy.
authors.affiliation: Department of Medical Genetics, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Liu
authors.forename: Xaoya
authors.initials: X
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Song
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D011836:Radiation Tolerance; D014183:Transplantation, Heterologous
chemical_list: D034741:RNA, Small Interfering; D054464:Peroxiredoxins