Objective  To investigate the proliferation inhibition and apoptosis -promoting effects of splice-switching oligonucleotides targeting the Bcl-x pre-mRNA (Bcl-x SSO) of the human glioma cell line U251.

  Methods  Bcl-x SSO was designed to bind tothe 5'-splice site of exon Ⅱ in Bcl-x pre-mRNA. An oligonucleotide targeted to aberrantly splice human β-globin intron was used as acontrol SSO. SSOs were modified using 2'-O-methoxyethyl and phosphorothioate, and were delivered together with lipofectamine intothe human glioma cell line U251 via cationic liposomes. The proliferation inhibition rate of the cell human cell line U251 was assessedvia MTT assay. Flow cytometry was performed to detect the apoptosis rate. Modulation from Bcl-xL to Bcl-xS was analyzed via reverse transcription polymerase chain reaction and Western blot.

  Results  The study showed that Bcl-x SSO caused proliferation inhibition and induced apoptosis in a dose-dependent manner in the human glioma cell line U251, whereas the control SSO did not show anyevident effect. The expression of Bcl-xL mRNA and protein increased, whereas the expression level of Bcl-xS mRNA decreased in thehuman glioma cell line U251 treated with Bcl-x SSO.

  Conclusion  The study demonstrated that Bcl-x SSO can induce apoptosis in human glioma cell line U251. The mechanism involves the redirection of Bcl-x splicing from Bcl-xl to Bcl-xs. Bcl-x SSOs have the potential to be used as anti-cancer drugs for glioma therapy.