PMID- 26323436
OWN - NLM
STAT- MEDLINE
DCOM- 20170427
LR  - 20211203
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 34
IP  - 5
DP  - 2015 Nov
TI  - Insulin-like growth factor binding protein-3 mediates interleukin-24-induced 
      apoptosis through inhibition of the mTOR pathway in prostate cancer.
PG  - 2273-81
LID - 10.3892/or.2015.4201 [doi]
AB  - IGF-binding protein-3 (IGFBP-3) has been shown to induce apoptosis in an 
      insulin-like growth factor (IGF)‑independent manner in various cell systems, 
      however, the underlying molecular mechanisms remain unknown. In the present 
      study, we showed that IGFBP-3 significantly enhanced interleukin-24 
      (IL-24)-induced cell death in prostate cancer (PC) cell lines in vitro. Both the 
      addition of IGFBP-3 to cell medium or the enforced expression of IGFBP-3 in the 
      PC cell line inhibited activation of mammalian target of rapamycin (mTOR). 
      Downregulation of mTOR/S6K reduced Mcl-1 protein expression and consequently 
      promoted sensitization to IL-24 treatment. Overexpression of Mcl-1 reduced the 
      level of cleaved poly(ADP-ribose) polymerase (PARP) induced by IL-24 and IGFBP-3, 
      suggesting that the IL-24-induced apoptosis is realized by way of Mcl-1. We then 
      showed that the combination of IL-24 and IGFBP-3 significantly suppressed PC 
      tumor growth in vivo. We propose that the IGFBP-3 and IL-24 non-toxic mTOR 
      inhibitors can be used as an adjuvant in the treatment of PC.
FAU - Du, Yuefeng
AU  - Du Y
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - Long, Qingzhi
AU  - Long Q
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - Shi, Ying
AU  - Shi Y
AD  - Department of Urology, Tongji Medical College Union Hospital, Huazhong University 
      of Science and Technology, Wuhan, Hubei, P.R. China.
FAU - Liu, Xiaogang
AU  - Liu X
AD  - School of Life Science and Technology, The Key Laboratory of Biomedical 
      Information Engineering of Ministry of Education, Xi'an Jiaotong University, 
      Xi'an, Shaanxi, P.R. China.
FAU - Li, Xudong
AU  - Li X
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - Zeng, Jin
AU  - Zeng J
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - Gong, Yongguang
AU  - Gong Y
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - Li, Lei
AU  - Li L
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - Wang, Xinyang
AU  - Wang X
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
FAU - He, Dalin
AU  - He D
AD  - Department of Urology, First Affiliated Hospital of Medical School, Xi'an 
      Jiaotong University, Xi'an, Shaanxi, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150813
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (IGFBP3 protein, human)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Interleukins)
RN  - 0 (MCL1 protein, human)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (interleukin-24)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Gene Expression
MH  - HEK293 Cells
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/genetics/*metabolism
MH  - Interleukins/genetics/*metabolism
MH  - Male
MH  - Mice, Nude
MH  - Myeloid Cell Leukemia Sequence 1 Protein/metabolism
MH  - Neoplasm Transplantation
MH  - Prostatic Neoplasms/*metabolism/pathology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4583521
EDAT- 2015/09/02 06:00
MHDA- 2017/04/28 06:00
PMCR- 2015/08/13
CRDT- 2015/09/02 06:00
PHST- 2015/05/14 00:00 [received]
PHST- 2015/07/07 00:00 [accepted]
PHST- 2015/09/02 06:00 [entrez]
PHST- 2015/09/02 06:00 [pubmed]
PHST- 2017/04/28 06:00 [medline]
PHST- 2015/08/13 00:00 [pmc-release]
AID - or-34-05-2273 [pii]
AID - 10.3892/or.2015.4201 [doi]
PST - ppublish
SO  - Oncol Rep. 2015 Nov;34(5):2273-81. doi: 10.3892/or.2015.4201. Epub 2015 Aug 13.