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Effects Of Glucagon - Like Peptide - 1 Analogues On Proliferation Of Prostate Cancer (LNCaP) And Breast Cancer (MCF - 7) Cell Lines

Posted on:2014-12-10Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q SangFull Text:PDF
GTID:2134330482962613Subject:Internal Medicine
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The effect of GLP-1 analogues on the proliferation of LNCaPObjective:1. To observe the effect of GLP-1 analogues exenatide and liraglutide on the growth of prostate cancer cells(LNCaP).2. To explore the molecular mechanism of apoptosis induced by GLP-1 analogues exenatide and liraglutide on LNCaP cells.Methods:1.Using the technique of cell culture in vitro, LNCaP cells were treated with different concentrations exenatide and liraglutide 0,1,10,100nmol/Lfor 24h.The effects on the cells were measured by CCK-8 assay and Hoechst33258/PI staining after the intervention.2.After LNCaP cells were treated with different concentrations of exenatide, expression levels of proteins which were relative to apoptosis such as bcl-2 and bax examined by Western-blot method.3. GLP-1R was detected on cell surface of LNCaP by RT-PCR method.Results:1.The proliferation rate of LNCaP cells was decreased in a dose-dependent after treatment with exenatide and the difference between groups was statistically significant (P<0.01). Liraglutide treatment to LNCaP cells resulted in a significant reduction in cell proliferation rate compared to the control group (P<0.01). Cell proliferation rate was significantly lower than that of exenatide when using the same concentrationliraglutideatland10nmol/L.Cellproliferationratecanbereducedto(63.75±6. 18)%and(52.75±6.13)%when treated respectively by exenatide and liraglutide.2. It was shown that LNCaP karyopyknosis was obvious apoptotic morphology and exenatideshowed a dose-dependent induction of apoptosis with different concentrations of exenatide intervention LNCaP cells after 24h with Hoechst33258/ PI staining.3. The level expression of bcl-2 was reduced and Bax expression was increased in a concentration-manner.The ratio of bcl-2/Bax was decressed with increasing dosage of exenatide.4. The apoptosis effect of exenatide and liraglutide on LNCaP cells in-depenfence of GLP-1R activation which was the same as β cells in pancreas.Conclusion:1. Exenatide and liraglutide could inhibit LNCaP cells proliferation and promote apoptosis.2. Exenatide and liraglutide could promote the occurrence of apoptosis in LNCaP cells by regulating the ratio of bcl-2 and Bax.3. The apoptosis effect of exenatide and liraglutide on LNCaP cells in-depenfence of GLP-1R activation which was the same as B cells in pancreas.The effect of GLP-1 analogues on the proliferation of human breast cancer line (MCF-7)Objective:To investigate the GLP-1 analogues and receptor agonist on the proliferation of breast cancer cells(MCF-7).Method:Using different concentrations (1,10,100,1000nmol/L) of liraglutide and exenatide intervention in MCF-7 respectively. CCK-8 assay were performed to test proliferation of MCF-7 after treatment 24,48,72 h.Results:1 There was no significant impact on the cell viability after treated by Liraglutidefor24h; The viability was decreased significantly with the treatment of 1000nmol group than that of 0,1,10 nmol groupaftertreatedfor48h.10,100,1000 nmol group was significantly lower than that of the control group, the groups showed no significant differenceafter72h. No significance was showed between 1000nmol 100nmol group at each time point.2MCF-7 was in a dose-dependent manner to inhibit the proliferation of MCF-7 compared to the control group with the intervention withl-100nmol/L concentrationsfor24hand48 h.3 Exenatide and liraglutide inhibition of MCF-7 cells was without significant time correlation.4Cell proliferation rate is less than the control group while the difference was not statistically significant; None difference among groups;1000nmol group had no significant effect on cell proliferation after 72h.Conclusion:Exenatide and liraglutide could inhibit the proliferation of MCF-7 cells.
Keywords/Search Tags:GLP-1 analogues, Prostate cancer, Apoptosis, LNCaP, GLP-1 receptors agonist, MCF-7
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