title: Hiwi knockdown inhibits the growth of lung cancer in nude mice.
abstract: Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of SSCloAldebr cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell SSCloAldebr cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.
authors.affiliation: Hainan Province Nongken Sanya Hospital, Sanya, Hainan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Lin-Jie
authors.initials: LJ
authors.lastname: Hu
authors.forename: Ze-Hui
authors.initials: ZH
authors.lastname: Fang
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: En-Hui
authors.initials: EH
authors.lastname: Shi
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Yang
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D060565:Argonaute Proteins; D007527:Isoenzymes; C421088:PIWIL1 protein, human; D034741:RNA, Small Interfering; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase