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  • Title: [Bcl-2 antisense oligodeoxynucleotide enhances araninosyl cytosine-induced apoptosis of primary leukemia cells].
    Author: Lei XY, Zhang H, He DM.
    Journal: Ai Zheng; 2002 Dec; 21(12):1301-4. PubMed ID: 12520735.
    Abstract:
    BACKGROUND & OBJECTIVE: The previous study has identified two novel antisense oligonucleotides (AS-ODN) of new target point in the translation initiation and the coding region of bcl-2 mRNA that could increase the sensitivity of HL-60 and K562 cells lines to etoposide, daunorubicin, and araninosyl cytosine (Ara-C). This study was designed to investigate whether the two novel bcl-2 AS-ODNs could increase Ara-C-induced apoptosis of cultured primary acute leukemia (AL) and chronic lymphocytic leukemia (CLL) Cells. METHODS: Cell surviving fraction was determined using the trypan blue dye exclusion assay. The expression levels of bcl-2 protein were assayed by immunofluorescence using fluorescein isothiocyanate label. Apoptosis was detected by Giemsa staining and flow cytometry. RESULTS: Treatment with the two AS-ODNs/Ara-C combination respectively for 48 h significantly inhibited the growth of AL and CLL cells. There was significant difference on AL and CLL cells survival between nonsense oligodeoxynucleotide(NS-ODN)/Ara-C combination and Ara-C treated cells alone (P < 0.05). It was found that the two AS-ODNs respectively combined with Ara-C could significantly downregulate bcl-2 protein expression (P < 0.05). There was a significant increase in apoptotic rates of AL or CLL cells after treatment with the two AS-ODNs respectively combined with Ara-C as respectively compared with the NS-ODN/Ara-C combination and Ara-C treated cells alone; and the effect had statistical difference (P < 0.05). Compared to the AS-ODN directed against the translation initiation of bcl-2 mRNA, the AS-ODN directed against the coding region showed stronger effect in the aspects of increasing the sensitivity of AL cells to Ara-C (P < 0.05). CONCLUSIONS: The two novel AS-ODNs of new target point in the translation initiation and the coding region of bcl-2 mRNA could enhance Ara-C induced apoptosis of AL and CLL cells.
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