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In Vitro Study Of The Effect Of GSK1838705A On The Proliferation And Apoptosis Of Pancreatic Cancer CAPAN-2 Cells

Posted on:2019-03-14Degree:MasterType:Thesis
Country:ChinaCandidate:H K WuFull Text:PDF
GTID:2404330566970222Subject:Surgery
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Background: Insulin like growth factor 1(IGF1)and receptor(IGF-1R)are the most important growth factors in the human body.Insulin like growth factor 1 receptor mediates the activity of IGF1,thereby promoting cell proliferation and metastasis,inhibiting cell apoptosis,and closely related to the occurrence and development of tumors.Related studies have shown that inhibition of the activity of IGF-1R can effectively control the proliferation and metastasis of various tumor cells in vivo,and promote the apoptosis of tumor cells.Pancreatic cancer is one of the most malignant malignancies in the human digestive system.It has the characteristics of rapid progression and poor prognosis.Its 5 year survival rate is only 1% to 3%,and its incidence is increasing gradually over the years.In pancreatic cancer,IGF-1R also plays a role in promoting tumor proliferation,metastasis and inhibiting tumor apoptosis.In this study,we used small molecule kinase inhibitor GSK1838705 A to inhibit the growth,metastasis and apoptosis of human pancreatic cancer cells by inhibiting the activity of insulin-like growth factor 1 receptor.Objective: Objective to investigate the antitumor effect of insulin-like growth factor 1receptor inhibitor GSK1838705 A on human pancreatic cancer cells.Methods: For different generations of human pancreatic cancer CAPAN-2 cells cultured in vitro;Cell Counting Kit-8(CCK-8)method to detect the effects of different concentrations of GSK1838705 A on pancreatic cancer CAPAN-2 cell proliferation;flow cytometry analysis of GSK1838705 A on apoptosis of pancreatic cancer CAPAN-2 cells;Western blot method to detect the effect of GSK1838705 A on pancreatic cancer cells after CAPAN-2 Bax and Cytochrome C the protein expression of CAPAN-2 cells after treatment;effects of GSK1838705 A on proliferation and migration of cell scratch test;Caspase-3 and Caspase-9 detection kits were used to determine cell apoptosis.Results: CCK-8 test results show that the different concentrations of GSK1838705 A could inhibit human pancreatic cancer CAPAN-2 cells with different degrees of proliferation,when the drug concentration was 10?M,the cell inhibition rate was up to98.29%;flow cytometry showed that GSK1838705 A induced apoptosis of CAPAN-2cells,and with the increase of GSK1838705 A concentration,apoptosis increased,when drug the concentration is 10?M,with more than 50% cell apoptosis;Western Bax and Cytochrome blot showed that the expression level of C protein increased;scratch test results showed that different concentrations of GSK1838705 A to the proliferation and migration of different degrees of inhibition of CAPAN-2 pancreatic cancer cells;and when the drug concentration is 5?M,in under the microscope can be observed in apoptotic cells more easily exfoliated vesicles;Caspase-3 and Caspase-9 apoptosis detection kit showed that GSK1838705 A has the effect of inducing apoptosis in pancreatic cancer CAPAN-2 cells,and shows a concentration dependence.Conclusion: Insulin like growth factor 1 receptor inhibitor GSK1838705 A can significantly inhibit the proliferation of human pancreatic cancer CAPAN-2 cells in vitro,induce apoptosis and inhibit cell migration,and play a significant anti-tumor role in human pancreatic cancer cells.
Keywords/Search Tags:GSK1838705A, pancreatic cancer, insulin-like growth factor 1 receptor, anti-tumor effect
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