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The Study Of HER2 Targeting Drug Sensitivity In Malignant Meningioma Cells

Posted on:2017-01-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:S S WangFull Text:PDF
GTID:1224330485499683Subject:Oncology
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Objective:To investigate the influence of HER2 targeted drugs on the proliferation,invasion and apoptosis of HER2 positive maligant meningioma cells, and to provide experimental basis for maligant meningioma individualized target therapy. The experiment for the treatment of recurrent and difficult to radical resection of malignant meningioma is of great significance.Methods:Experimental subject is HER2 moderate expression of malignant meningioma cell lines IOMM-Lee and weak HER2 expression of malignant meningioma cell lines CH157-MN cell lines,which HER2 m RNA level were proved by q PCR..The experiment was divided into five groups: the first was untreated group, the second was IOMM-Lee cell group, the third was IOMM-Lee-Tra group, the fourth was CH157-MN cell group, the fifth was CH157-MN-Tra group. After the application of HER2 targeting drug(Trastuzuma) contrast the change of proliferation and invasion of malignant meningioma cells. The MTT experiment was to investgate the proliferation ability and drug susceptibility of different groups in vitro. Cell cycle and apoptosis assays by flow cytometry were to investgate the cell ability of apotosis.Western Blot were used to detect the different expression of the apoptosis related protein Caspase-3 and PARP before and after using the drug. The nude mice has been observe the tumor formation before and after using the drug.Results:1. After using the HER2 targeting drug: a. The proliferation, invasion of the IOMM-Lee-Tra group was significantly reduced. CH157-MN-Tra drug group was not significantly reduced. The difference was statistically significant; b. IOMM- Lee-Tra group cell apoptosis rate was higher than IOMM- Lee group. The difference was statistically significant. However, there was no significant difference in CH157-MN-Tra drug group and CH157-MN group.2. Western Blot detected PARP and Caspase 3 protein expression in IOMM-Lee- Tra group was higher than IOMM- Lee group, while the HER2 protein expression in IOMM- Lee- Tra was lower than IOMM- Lee group. The difference has statistical significance. CH157- MN- Tra group compared with CH157- MN group the change of the three protein expression was not obvious. There was no statistically significant difference.3. Nude mice transplant tumor changes: IOMM- Lee- Tra group of tumor size smaller than IOMM- Lee group. However, there is no significant difference in CH157-MN-Tra group and the mock CH157-MN group.Conclusions:HER2 moderate expression of malignant meningioma cell lines IOMM-Lee is medium sensitivity to Trastuzuma,while CH157-MN is insensitivity.HER2 targeted drugs(Trastuzuma) may generate the tumor-suppression effect by means of reducing the expression of HER2 and increasing the expression of PRAP,Caspase-3.The experimental data may be provide experimental basis for clinical individualized treatment of malignant meningioma.
Keywords/Search Tags:Malignant meningioma, HER2, cell proliferation, targeted therapy, durg sensitivity
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