Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and isoverexpressed in various human tumors. This study aimed to determine whether an RNA interference-basedstrategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population ofSSCloAldebr cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containingU6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumormodel was generated by subcutaneously inoculating with lung cancer stem cell SSCloAldebr cells. After the tumorsize reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three timesa week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of HiwishRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNAplasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in miceadministered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressedexpression 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 strategyappeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAigene therapy in solid cancers.
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