Downregulation of mTOR by lentivirus inhibits prostate cancer cell growth.
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.
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Yue-Feng
YF
Du
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Qing-Zhi
QZ
Long
Department of Urology, Tongji Medical College Union Hospital, Huazhong University of Science & Technology Wuhan, Hubei, China.
Ying
Y
Shi
School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Xiao-Gang
XG
Liu
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Xu-Dong
XD
Li
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Jin
J
Zeng
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Yong-Guang
YG
Gong
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Xin-Yang
XY
Wang
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University Xi'an, Shaanxi, China.
Da-Lin
DL
He
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016086:Lentivirus; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
apoptosis; mTOR; prostatic carcinoma