本文選題：惡性腦膜瘤 + HER2　； 參考：《南昌大學(xué)》2016年博士論文

【摘要】：目的:探討HER2靶向藥物對HER2陽性的人惡性腦膜瘤細(xì)胞增殖、侵襲及凋亡的影響,以期為腦膜瘤個(gè)體化靶向治療提供實(shí)驗(yàn)依據(jù),對治療復(fù)發(fā)性及手術(shù)難以徹底切除的惡性腦膜瘤具有重要意義。方法:實(shí)驗(yàn)對象為經(jīng)q PCR檢驗(yàn)的HER2陽性表達(dá)的人惡性腦膜瘤細(xì)胞株IOMM-Lee和CH157-MN細(xì)胞株;其中前者為中度表達(dá),后者為弱表達(dá)。將實(shí)驗(yàn)分為五組:空白對照組、IOMM-Lee細(xì)胞組、IOMM-Lee-Tra用藥組、CH157-MN細(xì)胞組和CH157-MN-Tra用藥組。對比HER2靶向藥物(曲妥珠單抗)作用前后惡性腦膜瘤細(xì)胞在體內(nèi)、外增殖、侵襲及凋亡的變化;采用MTT檢測各組細(xì)胞增殖及體外藥物敏感性;transwell侵襲小室法檢測細(xì)胞侵襲能力;流式細(xì)胞術(shù)檢測各組細(xì)胞凋亡情況;Western Blot檢測凋亡相關(guān)蛋白Caspase-3、PARP在藥物作用前后表達(dá)的變化;裸鼠成瘤實(shí)驗(yàn),觀察成瘤情況,并對比藥物作用前后瘤體體積的變化。結(jié)果:1、HER2靶向藥物作用后:a、IOMM-Lee-Tra組在體外的增殖力及侵襲力均較IOMM-Lee組降低,兩者比較差異具有統(tǒng)計(jì)學(xué)意義;而CH157-MN-Tra組較CH157-MN組降低不明顯;b、IOMM-Lee-Tra組細(xì)胞凋亡率較IOMM-Lee組高,兩者差異具有統(tǒng)計(jì)學(xué)意義;CH157-MN-Tra組與CH157-MN組對比凋亡率差異無具有統(tǒng)計(jì)學(xué)意義;2、Western Blot檢測藥物作用后,PARP及Caspase-3蛋白在IOMM-Lee-Tra組表達(dá)均高于IOMM-Lee組,而HER2蛋白表達(dá)在IOMM-Lee-Tra組表達(dá)低于IOMM-Lee組,差異具有統(tǒng)計(jì)學(xué)意義;CH157-MN-Tra組與CH157-MN組比較,PARP、Caspase-3及HER2蛋白變化不明顯,差異無統(tǒng)計(jì)學(xué)意義。3、裸鼠體內(nèi)成瘤實(shí)驗(yàn)發(fā)現(xiàn),IOMM-Lee-Tra組瘤體體積較IOMM-Lee組縮小,差異具有統(tǒng)計(jì)學(xué)意義;CH157-MN-Tra組與CH157-MN組變化不明顯。結(jié)論:1、中度表達(dá)HER2的惡性腦膜瘤細(xì)胞IOMM-Lee對曲妥珠單抗具一定敏感性。而曲妥珠單抗作用于弱表達(dá)HER2的惡性腦膜瘤細(xì)胞CH157-MN的效果不明顯。2、曲妥珠單抗可能是通過增加PARP、Caspase-3蛋白表達(dá),降低HER2蛋白水平,從而對HER2陽性腦膜瘤細(xì)胞產(chǎn)生抑瘤作用。該實(shí)驗(yàn)數(shù)據(jù)可能為惡性腦膜瘤的臨床個(gè)體化治療提供實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective: to investigate the effects of HER2 targeting drugs on proliferation, invasion and apoptosis of HER2 positive human malignant meningioma cells in order to provide experimental evidence for individualized targeted therapy of meningiomas. It is of great significance for the treatment of recurrent malignant meningioma which is difficult to be resected completely. Methods: human malignant meningioma cell line IOMM-Lee and CH157-MN cell line with positive expression of HER2 were tested by Q PCR, in which the former was moderately expressed and the latter was weakly expressed. The experiment was divided into five groups: control group, IOMM-Lee cell group, IOMM-Lee-Tra group, CH157-MN cell group and CH157-MN-Tra group. The changes of proliferation, invasion and apoptosis of malignant meningioma cells in vivo, in vitro and in vitro were compared before and after treatment with HER2, and the invasion ability of malignant meningioma cells was detected by MTT assay and drug-sensitive transwell invasive chamber assay in vitro. Flow cytometry was used to detect apoptosis in each group. Western Blot was used to detect the expression of apoptosis-related protein Caspase-3PARP before and after drug treatment, and tumorigenesis was observed in nude mice before and after treatment, and the changes of tumor volume before and after drug treatment were compared. Results the proliferation and invasiveness of the IOMM-Lee group were significantly lower than that of the IOMM-Lee group, but the apoptosis rate of the CH157-MN-Tra group was lower than that of the CH157-MN group, but the apoptosis rate of the CH157-MN-Tra group was higher than that of the IOMM-Lee group. There was no significant difference in apoptotic rate between CH157-MN-Tra group and CH157-MN group. The expression of IOMM-Lee-Tra and Caspase-3 protein in IOMM-Lee-Tra group was higher than that in IOMM-Lee group, while the expression of HER2 protein in IOMM-Lee-Tra group was lower than that in IOMM-Lee group. The difference between CH157-MN-Tra group and CH157-MN group was not significant, but there was no significant difference in Caspase-3 and HER2 protein between CH157-MN-Tra group and CH157-MN group. The tumor volume of IOMM-Lee-Tra group was smaller than that of IOMM-Lee group. There was no significant difference between CH157-MN-Tra group and CH157-MN group. Conclusion IOMM-Lee of malignant meningioma cells with moderate expression of HER2 is sensitive to trotozumab. However, the effect of trotozumab on CH157-MN of malignant meningioma cells with weak expression of HER2 was not obvious. It may be that tratuzumab decreases the level of HER2 protein by increasing the expression of PARPnCaspase-3 protein, and thus has an inhibitory effect on HER2 positive meningioma cells. The experimental data may provide experimental basis for individual treatment of malignant meningioma.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R739.45

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