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Sirolimus Inhibits Human Pancreatic Carcinoma Cell Proliferation by a Mechanism Linked to the Targeting of mTOR/HIF‐1 Alpha/VEGF Signaling
Author(s) -
Wang Yu,
Zhao Qiu,
Ma Songlin,
Yang Fang,
Gong Yong,
Ke Changshu
Publication year - 2007
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540701646484
Subject(s) - sirolimus , pi3k/akt/mtor pathway , rptor , cancer research , vascular endothelial growth factor , cell growth , biology , mtorc2 , microbiology and biotechnology , chemistry , signal transduction , mtorc1 , vegf receptors , biochemistry
Sirolimus(SRL, Rapamuneâ, 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‐1α) 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‐1α/vascular endothelial growth factor (VEGF) pathway. Thus, the targeting of mTOR signaling has been exploited as a novel therapy for human cancers. IUBMB Life, 59: 717‐721, 2007