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        奧氮平通過誘導自噬抑制膠質瘤增殖
        來源: | 作者: | 發布時間:2013-11-8 17:03:22

        奧氮平通過誘導自噬抑制膠質瘤增殖
        王逸璇,徐舒青,陳相慧,劉睿思,梁中琴
        基金項目:國家自然科學基金項目(No. 81072656, 81102466, 81373430)
        作者簡介:王逸璇(1989-),女,碩士研究生,腫瘤藥理
        通信聯系人:梁中琴(1954-), 女, 教授,腫瘤藥理,神經藥理.

        (蘇州大學藥學院藥理專業,蘇州,215000)
        摘要:目的:本文旨在研究奧氮平(olanzapine)對膠質瘤細胞的抑制作用,及其可能的作用機制。方法:實驗選用膠質瘤T98 和LN229 細胞。MTT 法檢測不同濃度的奧氮平作用不同時間后對兩個膠質瘤細胞增殖率的影響。Western blot 檢測自噬相關蛋白LC3、p62 和凋亡相關蛋白Bcl-2 表達水平,免疫熒光檢測自噬熒光顆粒的形成。Hoechst 33258 染色以及Annexin V-FITC/PI 實驗檢測不同濃度奧氮平對細胞凋亡影響。MTT 和集落形成實驗分析自噬抑制劑3MA 對奧氮平抑瘤作用的影響。結果:MTT 結果顯示,奧氮平對LN229 和T98均有抑制作用。LC3、p62 的蛋白表達情況以及免疫熒光檢測LC3 的顆粒形成與分布情況都表明奧氮平誘導了自噬。Western blot 分析Bcl-2 蛋白表達、Hoechst 33258 染色實驗以及V-FITC/PI 染色實驗表明,奧氮平促進LN229 和T98 細胞凋亡。MTT 和集落形成實驗表明,自噬抑制劑3MA 減弱了奧氮平對這兩株膠質瘤細胞的增殖抑制作用。結論:奧氮平能夠抑制膠質瘤細胞生長,其抗膠質瘤作用的機制可能與自噬誘導相關。
        關鍵詞:藥理學;奧氮平;自噬;凋亡;膠質瘤;
        中圖分類號:R963
        Autophagy is involved in olanzapine-mediated cytotoxic effects in human glioma cells
        WANG Yixuan, XU Shuqing, CHEN Xianghui, LIU Ruisi, LIANG Zhongqin
        (Department of pharmocology, College of Pharmaceutical Sciences, Soochow University,SuZhou,215000)
        Abstract: Aim: The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy induction in glioma cells. Methods: Human glioma cell lines LN229 and T98 were tested in this study. MTT assay was used to determine cell viability of cultured glioma cells in response to olanzapine,. Western blotting was performed to analyze the expression levels of LC3, p62 and Bcl-2 proteins. Immunofluorescence using confocal microscopy was used to identify the formation of autophagosomes during autophagy. The apoptotic cells were observed using Hoechst 33258 staining followed by fluorescence microscopy, and the percentage of dead cells was quantified using annexin V-FITC/PI staining and flow cytometry. Results:LN229 and T98 cells were treated with olanzapine at a dose range of 0, 0.1, 0.2, 0.4, 0.6, 0.8 or1.0 mΜ for 24, 48 or 72h, respectively. As a result, the cell growth of LN229 and T98 were both suppressed in a concentration-dependent and time-dependent manner. Moreover, the punctates of microtubule-associated protein LC3, indicative of autophagy, and the expression level of membrane-bound LC3-II were significantly increased in olanzapine-treated glioma cells starting at48 h. The expression of protein p62, a substrate of autophagy, was decreased. The olanzapine-induced autophagy was also accompanied by a decrease of Bcl-2, leading to apoptosis as evidenced by an increased staining of Hoechst 33258 and Annexin V-FITC/PI of glioma cells.The growth inhibition of olanzaoine on glioma cells could be blocked by co-treatment with 3MA(2 mM). Conclusion: Olanzapine inhibits the growth of glioma cells accompanied by the induction of autophagy. The olanzapine-induced autophagy plays a tumor-suppressing role in glioma cells.
        Key words: pharmacology; olanzapine; autophagy; apoptosis; glioma

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