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[Bcl-2 antisense oligonucleotides suppress HL-60 cell growth in a SCID mouse mode]
Xiang-hua Lin1, Zhi-zhe Chen, Jing-juan Lin
1Fujian Institute of Hematology, Union Hospital Affiliated to Fujian Medical University, Fuzhou 350001, China. xianghua@pub1.FZ.fj.cn
Objective:
To study the effects of bcl-2 antisense phosphorothioate oligonucleotides (ASPO) on suppression of HL-60 cell growth in SCID mice and to investigate the feasibility of purging leukemia cells plus bcl-2 ASPO used in vitro.
Methods:
1 x 10(7) viable HL-60 cells were treated with 10 micro mol/L bcl-2 ASPO seven days before the intraperitoneal (IP) inoculation to the SCID mice, Treatment with sense oligonucleotides (SPO) was similar as for the controls. 35 days after the inoculation, all the SCID mice of both groups were sacrificed and their peripheral blood, bone marrow, liver and spleen were examined using half nested RT-PCR and histopathology for detecting the appearance and distribution of the HL-60 cells treated beforehand with antisense or sense oligonucleotides respectively.
Results:
ASPO could down regulate the expression of bcl-2 resulting in both inhibition of growth and induction of apoptosis in treated HL-60 cells, which failed to develop leukemia in SCID mice at all. However, SPO treated HL-60 cells still behaved their own ways and proliferated agressively, and developed leukemia at last.
Conclusion:
The bcl-2 ASPO enables to suppress HL-60 cell growth and prevent the development of leukemia in the SCID mice. The purging leukemia cells used are seemed liable in inhibiting the development of leukemia in SCID mouse model.
Insights
Bcl-2 antisense phosphorothioate oligonucleotides (ASPO) effectively suppressed HL-60 leukemia cell growth in SCID mice. This study demonstrates ASPO
Area of Science:
- Molecular biology
- Cancer research
- Oligonucleotide therapeutics
Context:
- Leukemia, specifically HL-60 cell line, poses a significant challenge in cancer therapy.
- The bcl-2 gene is a key regulator of apoptosis and is often overexpressed in various cancers, including leukemia.
- Antisense oligonucleotide technology offers a targeted approach to gene silencing.
Purpose:
- To evaluate the efficacy of bcl-2 antisense phosphorothioate oligonucleotides (ASPO) in suppressing HL-60 cell proliferation in a SCID mouse model.
- To investigate the feasibility of using bcl-2 ASPO for purging leukemia cells in vitro.
- To assess the impact of ASPO on bcl-2 gene expression, cell growth, and apoptosis.
Summary:
- HL-60 cells treated with bcl-2 ASPO demonstrated downregulated bcl-2 expression, leading to inhibited growth and induced apoptosis.
- These ASPO-treated cells failed to develop leukemia when inoculated into SCID mice.
- Conversely, control HL-60 cells treated with sense oligonucleotides (SPO) proliferated aggressively and induced leukemia.
Impact:
- bcl-2 ASPO shows significant potential in suppressing leukemia cell growth and preventing leukemia development in vivo.
- This research supports the therapeutic application of ASPO for leukemia treatment.
- The findings highlight the role of bcl-2 in leukemia pathogenesis and suggest ASPO as a viable anti-leukemic agent.