Prostate specific antigen promoter-driven adenovirus-mediated expression of both ODC and AdoMetDC antisenses inhibit prostate cancer growth
Prostate specific antigen promoter-driven adenovirus-mediated expression of both ODC and AdoMetDC antisenses inhibit prostate cancer growth
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DOI：
10.1007/s11670-010-0224-3
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发表时间：
2010-09
影响因子：
5.1
通讯作者：
Wei Li;H. Xiong;Yi-lin Hong;Chun-hua Zhang;Chang-chun Liu
中科院分区：
文献类型：
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作者：
Wei Li;H. Xiong;Yi-lin Hong;Chun-hua Zhang;Chang-chun Liu
ObjectiveTo generate recombinant adenovirus that could simultaneously express ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) antisenses specifically in prostate cancer cells, and evaluate its inhibitory effect on prostate cancerin vivo.MethodsFragments of ODC and AdoMetDC genes were generated by PCR, cloned into the pPGL-PSES, and then recombined with pAdEasy-1 vectors in AdEasy-1 cells. Ad-PSES-ODC-AdoMetDCas virus was produced in HEK293 cells. Following transfection with Ad-PSES-ODC-AdoMetDCas, the levels of ODC or AdoMetDC were determined by RT-PCR and western blot assays. The effect of Ad-PSES-ODC-AdoMetDCas treatment on tumor formation and growth was evaluated in xenograft models of prostate cancersin vivo.ResultsThe plasmid pAdEasy-PSES-ODC-AdoMetDCas was successfully constructed and the recombinant Ad-PSES-ODC-AdoMetDCas adenovirus was produced. Transfection with Ad-PSES-ODC-AdoMetDCas adenovirus significantly inhibited the expression of ODC and AdoMetDC genes specifically in prostate DU145 cells, but not H1299, HT29 and HepG2 cancer cells, and disrupted the ability of DU145 cells to form solid prostate cancerin vivo. Intratumoral treatment with Ad-PSES-ODC-AdoMetDCas adenovirus significantly inhibited the growth of engrafted prostate tumorsin vivo.ConclusionThe recombinant Ad- PSES-ODC-AdoMetDCas adenovirus specifically reduces the expression of both ODC and AdoMetDC genes in prostate cells and may be used for treatment of prostate cancers at the clinic.
