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Downregulation of mTOR by lentivirus inhibits prostate cancer cell growth.
- Source :
-
International journal of clinical and experimental pathology [Int J Clin Exp Pathol] 2014 Feb 15; Vol. 7 (3), pp. 923-31. Date of Electronic Publication: 2014 Feb 15 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Prostate cancer, one of the most lethal forms of urinary system cancer, remains resistant to currently available treatments. Therefore, novel mechanism and target-based approaches are needed for the management of this neoplasm. PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, the role of mTOR in prostate cancer is not well-established. Here, we demonstrate that mTOR is over-expressed in both clinical tissue specimens and cultured human prostate cancer cells when compared to normal prostate tissues, respectively. Further, mTOR gene knockdown via lentivirus mediated mTOR specific shRNA resulted in a significant decrease in the viability and growth of prostate cancer cells without affecting normal human prostate cells. In addition, mTOR inhibition resulted in a significant i) decrease in 4EBP1, S6K, PI3K and AKT protein, ii) increase in PARP protein of prostate cancer cells. Most importantly, mTOR inhibition triggered apoptosis and suppressed pancreatic carcinoma growth in vivo in a mouse xenograft model. We suggest that targeting of mTOR may be a viable approach for the treatment of prostate cancer.
- Subjects :
- Animals
Blotting, Western
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Gene Knockdown Techniques
Genetic Therapy methods
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Lentivirus
Male
Mice
RNA, Small Interfering
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Xenograft Model Antitumor Assays
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1936-2625
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of clinical and experimental pathology
- Publication Type :
- Academic Journal
- Accession number :
- 24695460