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Updated: May 26, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type A injection
Tiago Gorgal1, Ana Charrua, João F Silva
1Department of Urology, Hospital de São João, Alameda Professor Hernâni Monteiro, 4200-319, Porto-Portugal.
Background:
Onabotulinumtoxin A (OnabotA) injection has been investigated as a novel treatment for benign prostatic enlargement caused by benign prostatic hyperplasia. An OnabotA-induced volume reduction caused by sympathetic fibers impairment has been proposed as a potential mechanism of action. Our aim was to investigate the expression of apoptosis-regulating proteins in the rat prostate following OnabotA intraprostatic injection.
Methods:
Adult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group.
Results:
Saline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals.
Conclusions:
These results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.
Insights
Onabotulinumtoxin A (OnabotA) injection in rats promotes prostate cell death by increasing apoptosis-regulating proteins. This supports OnabotA’s potential for treating benign prostatic hyperplasia by affecting sympathetic nerve pathways.
Area of Science:
- Urology
- Molecular Biology
- Cell Biology
Background:
- Onabotulinumtoxin A (OnabotA) is explored for benign prostatic hyperplasia (BPH).
- A proposed mechanism involves OnabotA impairing sympathetic fibers, leading to prostate volume reduction.
- This study investigates OnabotA's effect on apoptosis-regulating proteins in rat prostates.
Purpose of the Study:
- To examine the expression of apoptosis-regulating proteins (Bax, Bcl-xL, caspase-3) in rat prostates after OnabotA injection.
- To elucidate the molecular mechanisms underlying OnabotA's potential therapeutic effects in BPH.
Main Methods:
- Adult Wistar rats received intraprostatic OnabotA or saline injections.
- Some OnabotA-injected rats received daily phenylephrine (PHE) treatment.
- Prostates were harvested after one week for immunohistochemical analysis of Bax, Bcl-xL, and caspase-3, with optical density measurements.
Main Results:
- OnabotA injection decreased Bcl-xL and increased Bax and caspase-3 expression in rat prostates compared to saline controls.
- Phenylephrine treatment reversed these changes, normalizing Bcl-xL, Bax, and caspase-3 levels.
- Quantitative analysis confirmed significant alterations in protein expression following OnabotA and PHE treatments.
Conclusions:
- OnabotA administration activates apoptotic pathways in the rat prostate.
- These findings support the hypothesis that OnabotA's mechanism involves sympathetic outflow impairment.
- The study provides molecular evidence for OnabotA's potential role in BPH treatment.
