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Expression Of CIP2A In Non-small Cell Lung Cancer And The Effect And Mechanism Of CIP2A In The Proliferation Of Lung Adenocarcinoma

Posted on:2018-03-15Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q WangFull Text:PDF
GTID:2334330536486450Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objectives:Lung cancer is the leading cause of tumor-related death.Lung cancer is mainly composed by non-small cell lung cancer(NSCLC)and small cell lung cancer(SCLC),with NSCLC accounting for 80% of all lung cancer.Although with the continuous development of medical progress,the current means of lung cancer treatment are rapidly developed(surgery,radiotherapy,chemotherapy and targeted therapy),the long-term survival of patients with lung cancer is still relatively poor.Therefore,there is an urgent need to find new and effective indicators that can be used to predict the prognosis of patients with NSCLC.CIP2 A plays an important role in the development of multiple tumors and in the transformation from normal cells to malignant cells by influencing the activity of PP2 A and the stability of C-MYC.CIP2 A also promotes anchor-independent growth and tumor formation in vivo.More and more studies have shown that CIP2 A is highly expressed in a variety of solid tumors and hematologic malignancies,and is associated with poor prognosis in a variety of cancer patients.This suggests that CIP2 A not only plays the role of cancer protein in human tumors,but may also be used as a clinical prognostic factor to determine the prognosis of cancer patients.This study aim to analyze the expression of CIP2 A in tumor tissues of NSCLC patients and analyze the relationship between the expression of CIP2 A and the clinical characteristics and prognosis of NSCLC patients.And further detect the role of CIP2 A in the proliferation of lung adenocarcinoma cells and explore its mechanism.Contents:Detect the expression of CIP2 A in NSCLC patients and analyze the relationship between CIP2 Aandthe clinical features and prognosis of NSCLC patients.Analyze proliferation and clonal ability,apoptosis and cell cycle of lung adenocarcinoma cells(H1975,A549 and PC-9)by inhibiting the expression of CIP2 A,and explore the role of CIP2 A in cell cycle.Methods:The expression of CIP2 A in tumor tissue of NSCLC patients was detected by immunohistochemistry and the relationship between the expression of CIP2 A and the clinical characteristics and prognosis of NSCLC patients was analyzed.The effect of CIP2 A on cell proliferation,cloning,apoptosis and cell cycle was investigated by in vitro cell analysis.The role of CIP2 A in cell cycle was explored.In this study,3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide(MTT)method was used to analyze the changes of cell proliferation after knockdown of CIP2 A.The changes of PP2 A activity were detected by malachite green method.Apoptosis of tumor cells after knockdown of CIP2 A was detected by Annexin V-FITC apoptosis assay.The changes of tumor cell cycle was detected by flow cytometry.The expression of CIP2 A,PP2A-C,AKT,p-AKT,C-MYC,P-27 and Cyclin D1 was detected by Western Blot after knockdown of CIP2 A.Results:1.The overexpression rate of CIP2 A in tumor tissue of NSCLC patients was higher than that of normal tissues.2.In patients with NSCLC,the overexpression of CIP2 A was higher in adenocarcinoma and stage IIIA patients.3.The overexpression of CIP2 A is associated with poor prognosis in patients with NSCLC.4.The expression level of CIP2 A in lung adenocarcinoma cells was higher than that in human bronchial epithelial cells.5.Inhibition of CIP2 A expression can significantly inhibit lung adenocarcinoma cell proliferation and cloning ability,and induce tumor cell apoptosis and cell cycle arrest.Conclusions:CIP2A is overexpressed in tumor tissue of NSCLC patients.The overexpression of CIP2 A is related to the poor prognosis of NSCLC patients and CIP2 A can be used as a predictor of poor prognosis of NSCLC.The expression level of CIP2 A in lung cancer cells was higher than that in human bronchial epithelial cells.The inhibition of CIP2 A expression could inhibit the proliferation and cloning ability of lung adenocarcinoma cells,and induce cell apoptosis and cell cycle arrest.
Keywords/Search Tags:Non-small cell lung cancer, DFS, OS, CIP2A, C-MYC, PP2A
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