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P62 Regulates The Malignant Progression Of Uveal Melanoma In Brain:A Proteomics Analysis And Verification

Posted on:2021-01-07Degree:MasterType:Thesis
Country:ChinaCandidate:F SunFull Text:PDF
GTID:2404330605973389Subject:Neurosurgery
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Background:Uveal melanoma(Uveal Melanoma,UM)brain metastasis is quite common,and the treatment is usually the same as UM in situ,while the effect is not ideal.The reason is that malignant progression of UM is regulated by the tumor microenvironment like all cancers.The differences between the regulatory molecules due to different microenvironments has become a consensus.Treatment on differentially expressed molecules to improve prognosis is current research concern.Differential proteomics analysis may accurately determine their existence.This article aims to use this method to optimize the UM regulatory protein of ectopic brain metastasis and observe the target treatment.Methods:Uveal melanoma cell 92.1 and uveal melanoma brain metastasis cell 92.1-A were used for the following experiments.Proteomics analysis of differentially expressed proteins of uveal melanoma carcinoma in situ and brain metastatic carcinoma;CCK 8 to detect cell proliferation;cell flow cytometry to detect cell cycle and apoptosis;qPCR to detect related gene expression;animal experiments to detect the effect and mechanism of combined treatment of chloroquine(CQ)and dacarbazine(DTIC)in uveal melanoma in vivoResults:Compared with the control group,cck-8 showed inhibition of cell proliferation,increased proportion of early apoptosis in flow cytometry reaction,decreased transwell migration,significantly decreased expression of p62 mRNA in qPCR reaction,decreased quality of transplanted tumor and p62 expression.Prism7.0 and image-pro Plus 6.0 showed significant differences(p<0.05).Conclusion:The malignant progression of uveal melanoma that grows ectopically in the brain,which is analysed by proteomics,is related to the high expression of p62 protein.Compared with the traditional treatment of melanoma,chloroquine,which is used to treat malaria,can inhibit p62 protein expression to a certain extent.And has a significant inhibitory effect on tumor growth in tumor-bearing mice.According to this,it provides convenience for further clinical transformation research,as chloroquine is the new application in cancer treatment.
Keywords/Search Tags:Uveal melanoma ectopic transplantation, Tumor proteomics, p62, Chloroquine, Darcabazine
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