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The Function Of Monoamine Oxidase A In Epithelial Ovarian Cancer

Posted on:2019-02-02Degree:MasterType:Thesis
Country:ChinaCandidate:T J LuoFull Text:PDF
GTID:2334330545476448Subject:Obstetrics and gynecology
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OBJECTIVE: Ovarian cancer is one of the most common cancers in the world,and its pathogenesis remains unclear.Oncogene activation and inactivation of tumor suppressor genes play an important role in the development of tumors.The literature reports that monoamine oxidase A(MAOA)is directly related to the pathological process of tumors.Aberrant MAOA genes are involved in almost all biological behaviors of cells,such as differentiation,proliferation,apoptosis,metabolism,invasion and migration.Through previous studies and database queries,it was found that the expression level of MAOA in ovarian cancer tissues and cells was significantly reduced,and the expression of MAOA was positively correlated with the survival.This article aims to study the expression of monoamine oxidase A(MAOA)in ovarian tissues and the function of epithelial ovarian cancer cells.METHODS:1.Clinical significance of low expression of monoamine oxidase A(MAOA)in epithelial ovarian cancer: A database analysis of the relationship between the expression of monoamine oxidase A(MAOA)and the clinicopathological features and prognosis of epithelial ovarian cancer.The expression of MAOA in epithelial ovarian cancer tissues was compared by RT-PCR.Epithelial ovarian cancer wax blocks with complete clinical data were collected to construct a tissue chip.Immunohistochemical method was used to analyze the clinicopathological features and prognosis of MAOA in ovarian epithelial carcinoma and evaluate the clinical significance of MAOA.2.Biological function of monoamine oxidase A(MAOA)in epithelial ovarian cancer cells: construction of stable transfection over-expression lentiviral vectors to examine their susceptibility to proliferation,apoptosis,migration,and chemotherapeutic drug susceptibility to epithelial ovarian cancer cells influences.Allograft xenograft models of nude mice were constructed and the size and weight of the transplanted tumors were compared to verify the effect of MAOA on proliferation of ovarian cancer cells in vivo.RESULT:1.Multiple database analysis showed that the expression of MAOA in ovarian cancer tissues was significantly lower than that of normal tissues: Analysis of Oncomine’s multiple ovarian cancer databases showed that ovarian cancer(ovarian carcinoma)and serous cystadenocarcinoma(ovarian serous cystadenocarcinoma)The m RNA expression of MAOA was significantly lower than that of normal tissues.Analysis of the GEO database(numbered GDS3592 [ACCN] and GDS2785)showed that compared with 12 normal epitheliums on the surface of the ovary,MAOA expression was significantly reduced in 12 cases of ovarian cancer(P=0.0026).The m RNA expression of MAOA in 9 cases of ovarian cancer tissues was significantly lower than that of 10 cases of ovarian cysts,P=0.0076.The analysis database Kaplan Meier-plotter(Ovarian Cancer)No.204388_s_st shows that the expression of MAOA is positively correlated with the patient’s progression-free survival time(PFS).2.Immunohistochemistry results showed low expression of MAOA in various types of epithelial ovarian cancer: immunohistochemical staining of tissue microarrays containing 101 ovarian cancer tissue chips and 127 benign ovarian cysts revealed MAOA Highly expressed in epithelial ovarian cancer tissues.The relationship between the expression of MAOA protein and clinicopathological features in 101 cases of ovarian cancer was analyzed by SPSS statistical software.The results showed that the expression of MAOA was closely related to epithelial ovarian cancer.It is closely related to the classification of ovarian cancer,among which clear cell carcinoma,high-grade serous ovarian cancer and advanced ovarian cancer have low expression levels,suggesting that it may be related to poor prognosis of ovarian cancer.3.MAOA can inhibit the proliferation and migration of epithelial ovarian cancer cells,promote its apoptosis,and increase the sensitivity of chemotherapeutic drugs: CCK8 cell proliferation experiments show that compared with the control group,MAOA overexpressing cells(OVCAR8 and ES2)have significant The differences in the patterns(p values were all<0.05);nude mice transplanted tumor experiments showed that the average tumor volume and tumor weight in the over-expressed MAOA group were 0.32±0.07(g)and 0.3852±0.2148(cm3),respectively.The volume and tumor weights were 1.298±0.298(g)and 2.4363 ± 1.1737(cm3),respectively.The tumor size and weight in both groups were statistically significant,with P values of 0.0001 and 0.003,respectively.The puncture test showed that the number of transfected cells in MAOA-overexpressing cells was significantly lower than that in the control group,and the difference was significant(all p<0.001).In vitro apoptosis experiments showed that the apoptosis of OVCAR8 and ES-2 cells was significantly increased after overexpression of MAOA.MTT assay showed that compared with the control group,the IC50 values and cell viability of MAOA overexpressed OVCAR8 cells and ES2 cells paclitaxel had no significant effects,the differences were not statistically significant(p values were> 0.05);IC50 values for cisplatin There was a significant difference from the viability of the cells(p values<0.05).CONCLUSIONS: 1.The markedly decreased expression of MAOA in ovarian cancer may be an important marker related to the prognosis of ovarian cancer.2.MAOA can inhibit epithelial ovarian cancer cell proliferation,migration,and promote apoptosis.3.MAOA enhances the survival of patients by enhancing the drug sensitivity of epithelial ovarian cancer cells to cisplatin.As a tumor suppressor gene,it is expected to become a new dosage form for the treatment of epithelial ovarian cancer.
Keywords/Search Tags:ovarian cancer, MAOA, tumor suppressor gene, prognosis, drug sensitivity
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