Inhibition of STAT3 expression by siRNA suppresses growth and induces apoptosis in laryngeal cancer

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:lsssml1990
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Aim:To determine the inhibitory effect of the synthetic STAT3 siRNA on theexpression of STAT3 gene in human laryngeal cancer cell lines Hep2 and to inves-tigate the effect of STAT3 siRNA on growth and apoptosis in Hep2 cells.Methods:A pair of DNA templates coding siRNA against STAT3-mRNA was synthesized toreconstruct plasmid of pSilencer1.0-U6 siRNA-STAT3.Hep2 cells were trans-fected with RPMI-1640 media (untreated),plasmid (empty),and STAT3 siRNA,respectively.Northern blot and Western blot analysis of STAT3 and pTyr-STAT3expression in Hep2 cells and Western blot analysis of Bcl-2 expression in the Hep2cell was performed 72 h after transfection.MTT,flow cytometry,and AO/EBassay were used for determination of cells proliferation and apoptosis in Hep2cells.Results:pTyr-STAT3 was markedly expressed in untreated Hep2 cells andthe vector-treated Hep2 cells,whereas pTyr-STAT3 expression was significantlyreduced in STAT3 siRNA-transfected Hep2 cells,indicating that STAT3 siRNAinhibited the activity of STAT3.Transfection of Hep2 cells with STAT3 siRNAsignificantly inhibited STAT3 expression at both mRNA and protein level in Hep2cells and the inhibition was characterized by time-dependent transfection.Treat-ment of Hep2 cells with STAT3 siRNA resulted in dose-dependent growth inhibi-tion of Hep2,this significantly increased apoptotic cell rate,and decreased Bcl-2expression level in Hep2 cells.STAT3 siRNA had an effect on induction of eitherearly or late stage apoptosis.Conclusion:This study demonstrates that STAT3siRNA effectively inhibits STAT3 gene expression in Hep2 cells leading to growthsuppression and induction of apoptosis in Hep2 cells.The use of siRNA tech-nique may provide a novel therapeutic approach to treat laryngeal cancer andother malignant tumors expressing constitutively activated STAT3. Aim: To determine the inhibitory effect of the synthetic STAT3 siRNA on theexpression of STAT3 gene in human laryngeal cancer cell lines Hep2 and to inves- tigate the effect of STAT3 siRNA on growth and apoptosis in Hep2 cells. Methods: A pair of DNA templates coding siRNA against STAT3-mRNA was synthesized to construct plasmids pSilencer1.0-U6 siRNA-STAT3.Hep2 cells were trans-fected with RPMI-1640 media (untreated), plasmid (empty), and STAT3 siRNA, respectively. Northern blot and Western blot analysis of STAT3 and pTyr-STAT3 expression in Hep2 cells and Western blot analysis of Bcl-2 expression in the Hep2cell was performed 72 h after transfection. MTT, flow cytometry, and AO / EBassay were used for determination of cells proliferation and apoptosis in Hep2 cells. Results: pTyr-STAT3 was markedly expressed in untreated Hep2 cells and the vector-treated Hep2 cells, whereas pTyr-STAT3 expression was significantlyreduced in STAT3 siRNA-transfected Hep2 cells, indicating that STAT3 siRNA was inhibited by the ac tivity of STAT3 Transfection of Hep2 cells with STAT3 siRNAs chemically-limited STAT3 expression at both mRNA and protein level in Hep2 cells and the inhibition was characterized by time-dependent transfection.Treat-ment of Hep2 cells with STAT3 siRNA resulted in dose-dependent growth inhibitori- tion of Hep2, this decreased increased the apoptotic cell rate, and decreased Bcl-2expression level in Hep2cells.STAT3 siRNA had an effect on induction of eitherearly or late stage apoptosis.Conclusion: This study demonstrates that STAT3siRNA inhibits STAT3gene expression in Hep2cells leading to growthsuppression and induction of apoptosis in Hep2 cells. The use of siRNA tech-nique may provide a novel therapeutic approach to treat laryngeal cancer andother malignant tumors expressing constitutively activated STAT3.
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