PMID- 17968710
OWN - NLM
STAT- MEDLINE
DCOM- 20080122
LR  - 20211203
IS  - 1521-6543 (Print)
IS  - 1521-6543 (Linking)
VI  - 59
IP  - 11
DP  - 2007 Nov
TI  - Sirolimus inhibits human pancreatic carcinoma cell proliferation by a mechanism 
      linked to the targeting of mTOR/HIF-1 alpha/VEGF signaling.
PG  - 717-21
AB  - Sirolimus(SRL, Rapamune(a), rapamycin) is a highly specific inhibitor of 
      mammalian target of rapamycin (mTOR). Sirolimus exerts its biological activity by 
      inhibiting the serine-threonine kinase mammalian target of rapamycin (mTOR), 
      which regulates important cellular processes such as control of cell cycle, cell 
      size, translation initiation and transcription. The ability of sirolimus to 
      inhibit cancer cell proliferation has led to efforts to develop rapamycin and 
      related mTOR inhibitors as anticancer agents. Here, we made mTOR as a controlling 
      target, using a new immunosuppressant named sirolimus, to investigate the 
      inhibitory effects of sirolimus on cell proliferation and the expression of mTOR, 
      Hypoxia-inducible factor-1 alpha(HIF-1alpha) and vascular endothelial growth 
      factor (VEGF) in human pancreatic carcinoma SW1990 cell line. Sirolimus is 
      effective in vivo against pancreatic carcinoma and demonstrates that the effect 
      of sirolimus on the inhibition of tumor cell proliferation is associated with the 
      suppression of the mTOR/HIF-1alpha/vascular endothelial growth factor (VEGF) 
      pathway. Thus, the targeting of mTOR signaling has been exploited as a novel 
      therapy for human cancers.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhao, Qiu
AU  - Zhao Q
FAU - Ma, Songlin
AU  - Ma S
FAU - Yang, Fang
AU  - Yang F
FAU - Gong, Yong
AU  - Gong Y
FAU - Ke, Changshu
AU  - Ke C
LA  - eng
PT  - Journal Article
PL  - England
TA  - IUBMB Life
JT  - IUBMB life
JID - 100888706
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Carcinoma
MH  - Cell Line, Tumor/drug effects
MH  - Cell Proliferation/*drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Pancreatic Neoplasms
MH  - Protein Kinases/genetics/*metabolism
MH  - Signal Transduction/*physiology
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
EDAT- 2007/10/31 09:00
MHDA- 2008/01/23 09:00
CRDT- 2007/10/31 09:00
PHST- 2007/10/31 09:00 [pubmed]
PHST- 2008/01/23 09:00 [medline]
PHST- 2007/10/31 09:00 [entrez]
AID - 783604526 [pii]
AID - 10.1080/15216540701646484 [doi]
PST - ppublish
SO  - IUBMB Life. 2007 Nov;59(11):717-21. doi: 10.1080/15216540701646484.