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Study On The Mechanism Of SHH Signaling Pathway Regulating Pancreatic Cancer Through Osteopontin

Posted on:2020-01-27Degree:MasterType:Thesis
Country:ChinaCandidate:H Q YangFull Text:PDF
GTID:2404330596497111Subject:Surgery
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Objective:Osteopontin(OPN)is closely related to human growth and development,and OPN is highly expressed in a large number of malignant tumors,even in pancreatic cancer.The high expression of OPN was caused at least in part by the abnormally activated Gli1,a terminal effector of the Sonic hedgehog signaling pathway(SHH).SHH signaling pathway is low or not expressed in mature body,but often highly expressed in tumor tissue.SHH signaling pathway is closely related to OPN.The exact role of OPN in the growth,survival and metastasis of pancreatic cancer cells and the reason for its high expression in this malignant tumor remain to be clarified.The purpose of this study was to select pancreatic cancer cells with high expression of OPN.In vitro experiments,the changes in the expression level of OPN after blocking SHH signal by Gli1 inhibitor GANT61 were investigated,so as to further influence the growth,migration,invasion and other malignant behaviors of pancreatic cancer cells.Methods:1.Select pancreatic cancer cells with high expression of OPN from pancreatic cancer cell lines bxpc-3,panc-1 and SW1990 as experimental cells by Polymerase Chain Reaction(Polymerase Chain Reaction)technique.2.Observe the expression levels of Gli1 and OPN by Western Blot after the adding GANT61 to pancreatic cancer cell in vitro cell experiments.3.Explore the changes in malignant behavior of pancreatic cancer cells after the addition of GANT61 by CCK8 assay,scratch assay,transwell migration assay and transwell invasion assay Results:1.OPN was generally expressed in pancreatic cancer,which was expressed in panc-1,bxpc-3 and SW1990,and the expression level of Panc-1 cell was the highest.Therefore,we selected the panc-1 cell as the experimental cell.2.The expression of Gli1 was decreased in panc-1 cells after GANT61 was used.Affected by this,the expression level of OPN also decreased.3.The expression of OPN was decreased after GANT61 inhibitor was used which reduced the ability of panc-1 cells to proliferate,migrate and invade.Conclusions:SHH signaling pathway is very active in a variety of malignant tumors.We inhibited the expression of SHH signaling pathway by inhibiting Gli1.In this case,we find that the expression level of OPN is reduced.At the same time,the proliferation,migration and invasion ability of pancreatic cancer cells panc-1 are decreased.The inhibition of SHH pathway can reduce the expression of OPN in pancreatic cancer cells and inhibit the growth and metastasis of Panc-1.
Keywords/Search Tags:pancreatic cancer, OPN, Gli1, Sonic hedgehog pathway
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