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BCL2 antisense transcripts decrease intracellular Bcl2 expression and sensitize LNCaP prostate cancer cells to
X B Shi1, P H Gumerlock, J T Muenzer
1Dept of Urology, University of California, Davis, School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA.
Abstract:
Prostate cancer (CaP) is the most commonly diagnosed cancer of aging men and the second leading cause of male cancer death in the United States. At present, no effective therapy is available for treating hormone independent CaP. Since Bcl2 is believed to play a role in protecting CaP cells from apoptosis, we investigated the effects of down-regulating Bcl2 expression on CaP cells. Genetically engineered LNCaP sublines were established by stably transfecting LNCaP cells with BCL2 antisense (BCL2-AS) transcript-expressing plasmids. Western blotting analysis showed that intracellular Bcl2 protein was decreased by 50-60% in BCL2-AS-transfected LNCaP cells. Expression of the antisense transcripts resulted in 50% growth inhibition of LNCaP cells in response to androgen withdrawal and markedly sensitized these cells to Adriamycin-induced apoptosis. These results suggest that down-regulation of Bcl2 protein using BCL2-AS transcripts could be exploited for improved treatment of advanced CaP.
Insights
Down-regulating Bcl2 protein expression in prostate cancer (CaP) cells using BCL2 antisense transcripts inhibits CaP cell growth and increases sensitivity to apoptosis. This approach may offer a new therapy for advanced CaP.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Prostate cancer (CaP) is a leading cause of cancer death in aging men.
- Currently, no effective treatments exist for hormone-independent CaP.
- Bcl2 protein is implicated in protecting CaP cells from programmed cell death (apoptosis).
Purpose of the Study:
- To investigate the effects of down-regulating Bcl2 expression on prostate cancer cells.
- To assess the therapeutic potential of targeting Bcl2 in advanced CaP.
Main Methods:
- Established genetically engineered LNCaP sublines by transfecting with BCL2 antisense (BCL2-AS) transcript-expressing plasmids.
- Utilized Western blotting to quantify intracellular Bcl2 protein levels.
- Evaluated cell growth inhibition under androgen withdrawal and sensitivity to Adriamycin-induced apoptosis.
Main Results:
- BCL2-AS transfection reduced intracellular Bcl2 protein by 50-60%.
- Antisense transcript expression led to 50% growth inhibition of LNCaP cells during androgen withdrawal.
- BCL2-AS significantly sensitized LNCaP cells to Adriamycin-induced apoptosis.
Conclusions:
- Down-regulation of Bcl2 protein via BCL2-AS transcripts effectively inhibits prostate cancer cell growth.
- Targeting Bcl2 expression enhances apoptosis sensitivity in CaP cells.
- BCL2-AS transcripts represent a potential therapeutic strategy for advanced prostate cancer.