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Published on: March 6, 2018
Translocator protein blockade reduces prostate tumor growth
Arlee Fafalios1, Ardavan Akhavan, Anil V Parwani
1Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Summary
Translocator protein (TSPO) is upregulated in prostate cancer, promoting tumor growth. The drug lorazepam, a TSPO ligand, demonstrated anticancer effects by inhibiting proliferation and inducing cell death in prostate cancer models.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Transmembrane protein TSPO is implicated in epithelial tumor progression.
- TSPO gene expression is elevated in steroid biosynthesis, neurodegenerative diseases, and cancers.
- Overexpression of TSPO contributes to pathological conditions, including cancer progression.
Purpose of the Study:
- To investigate TSPO expression and biological significance in prostate cancer.
- To evaluate the anticancer potential of lorazepam, a TSPO ligand, in prostate cancer.
Main Methods:
- Immunohistochemical analysis of TSPO expression in human prostate cancer tissues using tissue microarrays.
- In vitro and in vivo studies utilizing cell proliferation assays, apoptosis ELISA, and xenograft models.
- Assessment of TSPO ligand effects (lorazepam, PK11195) on prostate cancer cells.
Main Results:
- TSPO expression is significantly increased in prostatic intraepithelial neoplasia, primary prostate cancer, and metastases compared to normal or benign tissues.
- TSPO levels correlate with prostate cancer progression, including Gleason sum and stage, with highest expression in metastases.
- Lorazepam exhibits significant antiproliferative and proapoptotic effects in vitro and in vivo, particularly in cells overexpressing TSPO.
Conclusions:
- TSPO plays a survival role in prostate cancer, and its inhibition induces tumor cell death.
- Blocking TSPO function represents a potential therapeutic strategy for prostate cancer.
- Benzodiazepines, such as lorazepam, show promise as novel therapeutic agents for prostate cancer.
