Insulin-like growth factor 1 inhibits autophagy of human colorectal carcinoma drug-resistant cells via the protein kinase B/mammalian target of rapamycin signaling pathway

BackgroundMetformin is a well-tolerated biguanide drug used for decades to treat type 2 diabetes mellitus. In recent years, long-term administration of metformin has been found to reduce carcinogenic risk for cancers derived from various tissues. However, its cellular and molecular mechanisms of anticancer action in the endometrial cancer (EC) have not yet been fully elucidated.Patients and MethodsSixty patients diagnosed as endometrial carcinoma were grouped into (n = 30) and non-treatment mixed (n = 30) for analysis. Thirty healthy donors are control groups. We attempt to investigate the interaction of metformin, insulin-like growth factor 1 (IGF-1) expression, and phosphorylated mammalian target of rapamycin (p-mTOR) and AMP-activated protein kinase (p-AMPK).ResultsWe found that high IGF-1 plasma concentrations in women with EC were reversed by conventional antidiabetic doses of metformin in the present work. In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC.ConclusionsThis pilot trial presents biological evidence consistent with antiproliferative effects of metformin in women with EC in the clinical setting.

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Insulin Receptor Substrate-2 Proteasomal Degradation Mediated by a Mammalian Target of Rapamycin (mTOR)-induced Negative Feedback Down-regulates Protein Kinase B-mediated Signaling Pathway in β-Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m412179200 ◽

2004 ◽

Vol 280 (3) ◽

pp. 2282-2293 ◽

Cited By ~ 102

Author(s):

Isabelle Briaud ◽

Lorna M. Dickson ◽

Melissa K. Lingohr ◽

Jill F. McCuaig ◽

John C. Lawrence ◽

...

Keyword(s):

Protein Kinase ◽

Insulin Receptor ◽

Signaling Pathway ◽

Negative Feedback ◽

Protein Kinase B ◽

Mammalian Target Of Rapamycin ◽

Proteasomal Degradation ◽

Target Of Rapamycin ◽

Insulin Receptor Substrate ◽

Β Cells

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Gambogic Acid Affects Ribosomal Occurrence in Glioma Cells by Downregulating the Phosphoinositide Kinase-3/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.17425 ◽

2020 ◽

Vol 20 (6) ◽

pp. 3361-3372 ◽

Cited By ~ 1

Author(s):

Guoxuan Luo ◽

Shengqiang Jiang ◽

Xu Zhang ◽

Yunzhi Ling ◽

Hengshan Luo ◽

...

Keyword(s):

Protein Kinase ◽

Signaling Pathway ◽

Protein Kinase B ◽

Mammalian Target Of Rapamycin ◽

Glioma Cells ◽

Mtor Signaling ◽

Target Of Rapamycin ◽

Gambogic Acid ◽

Mtor Signaling Pathway ◽

Phosphoinositide Kinase

Gambogic acid (GA) is a natural compound with a polyprenylated xanthone structure that has antiinflammatory, antioxidant, and neuroprotective properties and acts as a chemopreventive agent. GA exhibits anti-tumor, antimicrobial, and anti-proliferative effects on cancer cells. In the current study, the effect of GA on phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Cell viability and apoptosis were evaluated by MTT and Annexin V/PI Double Staining. The expressions of P38, AKT, and mTOR were evaluated by western blot and qRT-PCR, respectively. MagBeads Total RNA Extraction Kit was used to isolate cell tissue RNA. GA decreased the phosphorylation of P38, AKT, and mTOR. Inhibitors of PI3K (LY294002) enhanced the phosphorylation of P38, AKT, and mTOR. GA reduced the phosphorylation of ribosomal protein precursors (Pre) and upstream binding factor (UBF), and insulin-like growth factor I (IGF-1) further enhanced the cell proliferation and expression of Pre and UBF. These results suggested that downregulation of PI3K/AKT/mTOR signaling pathway may be an important mediator in GA-affected ribosomal occurrence in glioma cells.

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