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Study On Dexamethasone Disrupts Cytoskeleton Organizations And Cell Migrations Of T47D Human Breast Cancer Cells By Modulating AKT/MTOR/RHOA Pathway

Posted on:2016-11-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:X G MengFull Text:PDF
GTID:1224330482963722Subject:Rehabilitation medicine and physical therapy
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Background:Breast cancer is one of common malignant tumors that serious harm to women’s lives and health security. Although since 1990, the mortality of breast cancer in worldwide has been reduced by 34%, and 5-year survival rate have increased by 90%, but the mortality rate of breast cancer was still the second highest in all female malignancies. Trend of breast cancer is not optimistic. In recent decades, the age of onset of breast cancer patients was gradually becoming younger, and the incidence rate increased year by year, the degree of malignancy was also rising. The academic world for the cause of breast cancer incidence, pathogenesis and the transfer mechanism were still not clear, and thus brought to a very big impact in early prevention, diagnosis, treatment and prognosis of breast cancer, and also became an obstacle to the development of drugs to cure in breast cancer.Objective:In this study, the expression of AKT, mTOR, RhoA mRNA and protein have been detected in breast cancer tissues, and analyzed the correlation between the expression of AKT mTOR RhoA and clinical pathological parameters, determined whether it could be used as a index in clinical diagnosis and prognosis.Methods:(1) The expression of AKT, mTOR, RhoA mRNA in breast cancer tissues and corresponding normal tissues have been detected by quantitative PCR, which were from 50 cases of breast cancer patients;(2) We detected the expression of AKT, mTOR, RhoA protein in breast cancer tissues and corresponding normal tissues by western blot, which were from 50 cases of breast cancer patients;(3) We analyzed the correlation between the expression of AKT, mTOR, RhoA protein and clinical pathological parameters, determined whether it could be used as a target in clinical diagnosis and prognosis.Result:(1) Quantitative PCR results showed that the expression of AKT, mTOR, RhoA mRNA in breast cancer tissues were significantly higher than them in corresponding normal tissues (P<0.01);(2) Western blot results showed that the expression of AKT, mTOR, RhoA protein in breast cancer tissues were significantly higher than them in corresponding normal tissues (P<0.01);(3) The expression of AKT, mTOR, RhoA protein had nothing to do with the age, tumor size of patients (P> 0.05), but had something to do with the pathological staging, brain metastases and bone metastasis (P<0.05).Conclusion:AKT, mTOR, RhoA play a role as cancer-promoting genes in the occurrence, development and metastasis of breast cancer.Background:Dexamethasone (dexamethasone, Dex) belongs to adrenocorticotropic hormone, is commonly used in clinical medicine, which has anti-inflammatory, immuno-suppression, anti-shock and increase stress and other effects, it widely used in the diseas treatment. In the clinical treatment of malignant tumors, Dex can reduce the toxicity of chemotherapy drugs to the hematopoietic system, while reducing the side effects of chemotherapy drugs of bone marrow suppression. A large number of studies have confirmed that drug combination with Dex can increase sensitivity to chemotherapy, and thus it played a better effect in anti-tumor. For these reasons, Dex was widely used in the treatment of malignancies. Studies have shown that, Dex combined with other chemotherapy drugs was effective in treating breast cancer and improve survival.Objective:This study was designed to investigate the mechanism of the regulating of AKT/ Mtor/RhoA signaling pathway by Dex in the cytoskeleton structure and migration, in order to open a new avenue in treatment of breast cancer.Methods:We treated the T47D cells with different concentrations of Dex. We detected the ability of migration by cell scratch assay, cell proliferation was detected by MTT assay, apoptosis was detected by flow cytometry; the effect on the cytoskeleton was detected by immunofluorescence; the expression of AKT, p-AKT, mTOR, p-mTOR, RhoA protein were detected by western blot.Result:(1) Dex could inhibit the T47D migration in a dose-dependent manner;(2) Dex had no significant effect on cell proliferation and apoptosis of T47D cells;(3) Dex could affect the skeleton structure of T47D cells;(4) Dex could inhibit the expression of p-AKT, p-mTOR RhoA protein, but does not affect the expression of AKT and mTOR protein.Conclusion:Dex can significantly inhibit migration of T47D cells, the process was regulated with AKT/mTOR/RhoA signaling pathway and then destroyed T47D cell skeleton structure.
Keywords/Search Tags:breast cancer, AKT, mTOR, RhoA, Dexamethasone, AKT/mTOR/RhoA signaling pathway, cytoskeleton, migration
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