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The Research of Inhibitory Effects of Sirolimus on Cell Proliferation and Expression of HIF-1α and VEGF Through mTOR Signal Pathway in Human Pancreatic Carcionma SW1990 Cells
Author: WangYu
Tutor: ZhaoQiu
School: Huazhong University of Science and Technology
Course: Digestion within the science
Keywords: Sirolimus Pancreatic Cancer mTOR HIF-1α VEGF
CLC: R735.9
Type: Master's thesis
Year: 2007
Downloads: 127
Quote: 0
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Abstract
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Purpose : Sirolimus is a specific inhibitor of a mammalian target of rapamycin , a recent study found that it has a good anti-tumor effect , but its mechanism is not yet fully elucidated , the experiment through the study of sirolimus cultured human pancreatic cancer cell line SW1990 proliferation and mTOR inhibition of HIF - 1α, VEGF gene explore mTOR as a target in the treatment of pancreatic cancer may be the mechanism of intracellular signal transduction . Method : cultured pancreatic cancer SW1990 cells under hypoxic conditions in vitro , exogenous administration of different concentrations of sirolimus (0.01 nmol/L-100000 nmol / L) to stimulate cell 24h , MTT assay different concentrations of the drug for pancreatic cancer cell proliferation the impact . Semi-quantitative RT-PCR analysis of sirolimus SW1990 cells mTOR, HIF-1α and VEGF mRNA expression . Western blot detection of different concentrations of drugs to stimulate the SW1990 cells of mTOR , HIF -1α and VEGF protein expression changes . Results : sirolimus significantly inhibit the proliferation of pancreatic cancer cells SW1990 , the inhibition rate increased with increasing drug concentration . With the increase in the concentration of sirolimus role of mTOR and VEGF mRNA expression levels in SW1990 cells showed a downward trend , the experimental group and the control group , the difference was statistically significant ( P lt; 0.05 ) ; while sirolimus the concentration level expression of HIF-1αmRNA no significant impact . Sirolimus significantly inhibited the SW1990 cells mTOR , HIF - 1α, VEGF protein expression , the inhibitory effect of the largest group of its concentration maximum . Conclusion : Under hypoxic conditions , the sirolimus via mTOR signal transduction pathway down HIF-1α protein expression in pancreatic cancer SW1990 cells , thereby inhibiting the VEGF gene transcription induced apoptosis , which may sirolimus one of the anti - tumor mechanism .
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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Pancreatic tumors
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