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Separate And Combined Use Of2-Deoxyglucose And3-Bromo-Pyruvate Inhibits Colorectal Cancer Cell Proliferation

Posted on:2014-02-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:H J XiaoFull Text:PDF
GTID:1224330395496572Subject:Surgery
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Objective To investigate the separate and combined use of2-DG and3-BrPA, inhibit the proliferation ofcancer cells. Methods2-DG and3-BrPA, when used alone, were taken the four molecular concentrations(0.3,1,4,18mM) and (6.25,25,100,400μM). The two drugs when combined with,2-DG is still taking theabove-mentioned gradient of concentration, while the3-BrPA take a fixed concentration of25μm or100μm, a separate negative control group (with an equal volume of culture medium). MTT assay differentconcentrations of2-DG (0,0.3,1,4,18mmol/L) and the3-BrPA inhibition of cancer cell proliferationunder normoxic and anaerobic state. HIF-1α expression in normoxic and anaerobic state situations anddifferent concentrations of2-DG and of3-BrPA role of HIF-1α and HK-II expression was detected byWestern Blot cancer cell. Use ATP detection kit different concentrations of2-DG and3-BrPA undernormoxic and anaerobic environments cancer cell ATP generation and detection cell to generate theamount of fumaric acid change. Results Under normoxic and anaerobic conditions, a separate2-DG and3-BrPA, significantly inhibited the proliferation of rectal cancer, the combined use of the two drugs inhibitthe proliferation more pronounced. Western Blot analysis found that the effect of the2-DG and3-BrPA,colon cancer cells in HIF-1α, HK-II expression was significantly reduced. Singly or in combination of2-DG and the3-BrPA the colon cancer cells in the ATP and the amount of lactic acid, while increasing thegeneration amount of the fumaric acid. Conclusions2-DG and3-BrPA, aerobic metabolism of glucoserecovery by inhibiting colon cancer cell glycolysis reduces its ATP generate plays proliferation inhibition.2-DG and3-BrPA reduce the expression of HIF-1and glycolytic key enzyme in glycolysis and inhibitcolorectal cancer cells glycolysis.
Keywords/Search Tags:2-DG, 3-BrPA, colorectal cancer, proliferation, Warburg Effect
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