PMID- 24944633
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 8
IP  - 1
DP  - 2014 Jul
TI  - Interferon-alpha enhances the susceptibility of renal cell carcinoma to rapamycin by 
      suppressing mTOR activity.
PG  - 267-273
AB  - The aim of the present study was to investigate the antiproliferative effects of 
      interferon (IFN)-alpha and rapamycin (RPM) on renal cell carcinoma (RCC) cells and 
      examine the synergistic growth suppression conferred by IFN-alpha and RPM. The 
      effects of IFN-alpha and/or RPM on RCC cells were determined using a WST-1 assay and 
      the synergy of IFN-alpha and RPM against three RCC cell lines was analyzed with 
      isobolographic analysis. The expression of mammalian target of rapamycin (mTOR) 
      was downregulated by RNAi, and the expression and phosphorylation of proteins in 
      the mTOR pathway following treatment with IFN-alpha and/or RPM was examined by 
      western blot analysis. The observations indicated that IFN-alpha significantly 
      increased the susceptibility of RCC cells to RPM and the synergistic effect of 
      IFN-alpha and RPM against RCC cells was confirmed in all three RCC cell lines. The 
      mTOR pathway was shown to be associated with the synergistic effect of IFN-alpha and 
      RPM against RCC. IFN-alpha and RPM alone decreased the phosphorylation of mTOR, p70 
      S6 kinase, S6 and 4E binding protein 1, and IFN-alpha significantly enhanced the 
      RPM-induced suppression of the mTOR pathway. However, in RCC cells with low mTOR 
      activity, the synergy of IFN-alpha and RPM was eliminated. Therefore, the results of 
      the present study indicate that the mTOR pathway plays an important role in the 
      synergistic effect of IFN-alpha and RPM against RCC cells. Thus, mTOR may serve as an 
      effective therapeutic target in the treatment of advanced RCC.
FAU - Han, Xiao
AU  - Han X
AD  - Department of Urology, Beijing Friendship Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Shang, Donghao
AU  - Shang D
AD  - Department of Urology, Beijing Friendship Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Han, Tiandong
AU  - Han T
AD  - Department of Urology, Beijing Friendship Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Xu, Xiuhong
AU  - Xu X
AD  - Department of Urology, Beijing Friendship Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
FAU - Tian, Ye
AU  - Tian Y
AD  - Department of Urology, Beijing Friendship Hospital, Capital Medical University, 
      Beijing 100050, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20140425
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC4061221
OTO - NOTNLM
OT  - interferon-alpha
OT  - mammalian target of rapamycin
OT  - rapamycin
OT  - renal cell carcinoma
EDAT- 2014/06/20 06:00
MHDA- 2014/06/20 06:01
PMCR- 2014/04/25
CRDT- 2014/06/20 06:00
PHST- 2013/10/29 00:00 [received]
PHST- 2014/03/19 00:00 [accepted]
PHST- 2014/06/20 06:00 [entrez]
PHST- 2014/06/20 06:00 [pubmed]
PHST- 2014/06/20 06:01 [medline]
PHST- 2014/04/25 00:00 [pmc-release]
AID - etm-08-01-0267 [pii]
AID - 10.3892/etm.2014.1691 [doi]
PST - ppublish
SO  - Exp Ther Med. 2014 Jul;8(1):267-273. doi: 10.3892/etm.2014.1691. Epub 2014 Apr 
      25.