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Anticancer Res. 1997 Sep-Oct;17(5A):3307-12.

Development of a hammerhead ribozyme against BCL-2. II. Ribozyme treatment sensitizes hormone-resistant prostate cancer cells to apoptotic agents.

Author information

1
Department of Urology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Abstract

BACKGROUND:

Several lines of evidence strongly implicate a crucial role for the apoptosis suppressing bcl-2 oncogene in the genesis of hormone-refractory human prostate cancer. By efficiently destroying the intracellular bcl-2 mRNA, one might be able to make the prostate cancer cell responsive again to conventional apoptotic stimuli such as androgen withdrawal. To achieve this end, we have devised a catalytic antisense RNA strategy (Ribozyme) for bcl-2 and evaluated its gene therapeutic potential.

METHODS AND RESULTS:

Bcl-2 overexpressing LNCaP prostatic carcinoma cells (LNCaP/bcl-2) were transfected with the anti-bcl-2 ribozyme RNA using a polyamine-based transfection reagent and the reduction in the intracellular bcl-2 mRNA levels was followed by a ribonuclease protection assay. Using a cell viability assay, prior ribozyme transfection and subsequent application of apoptotic stimuli such as serum starvation or phorbol ester treatment caused a 30% increase in cell death by apoptosis than with these apoptotic stimuli alone.

CONCLUSIONS:

The results obtained strongly support the ability of a potential anti-bcl-2 ribozyme therapy to synergize with other agents in inducing apoptosis of hormone-resistant human prostate cancer cells.

PMID:
9413164
[Indexed for MEDLINE]

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