Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:lg7519
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Aim:To investigate the effect of antisense oligodeoxynucleotides (ASODN) tar-geting Pim-2 on cell proliferation of DU-145 cells.Methods:Three ASODN target-ing Pim-2 were designed and synthesized.After transfection with ASODN,cellproliferation was analyzed using an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium,inner salt] assay.Inaddition,Pim-2 mRNA,protein levels,and cell cycles were examined.Results:The ASODN designed and synthesized by our laboratory significantly reducedPim-2 mRNA level and protein content in DU-145 cells.After transfection withASODN for 48 h,a marked reduction in cell viability was observed in DU-145 cellsin a dose-dependent manner.No remarkable apoptosis occurred in ceils treatedwith ASODN compared with control cells.However,it should be noted that G_1phase arrest was clearly observed in ASODN-treated cells.Conclusion:ASODNtargeting Pim-2 resulted in a marked reduction in DU-145 cell proliferation,andinduction of G_1 phase cell cycle arrest is one of the important mechanisms forASODN to reduce cell growth.Moreover,antisense inhibition of Pim-2 expres-sion provides a new promising therapy target for prostate cancer. Aim: To investigate the effect of antisense oligodeoxynucleotides (ASODN) tar-geting Pim-2 on cell proliferation of DU-145 cells. Methods: Three ASODN target-ing Pim-2 were designed and synthesized. After transfection with ASODN, cellproliferation was using an MTS [3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazolium, inner salt] assay.Inaddition, Pim-2 mRNA, Results: The ASODN designed and synthesized by our laboratory significantly reduced PIM-2 mRNA level and protein content in DU-145 cells. After transfection with ASODN for 48 h, a marked reduction in cell viability was observed in DU-145 cellsin a dose-dependent manner. No significant apoptosis occurred in ceils treated with ASODN compared with control cells. However, it should be noted that G_1phase arrest was clearly observed in ASODN-treated cells. Conlusion: ASODNtargeting Pim-2 resulted in a marked reduction in DU-145 cell proliferation, and induction of G_1 phase cell cycle arrest is one of the important mechanisms for ASODN to reduce cell growth. Moreover, antisense inhibition of Pim-2 expres-sion provides a new promising therapy target for prostate cancer.
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