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米托恩坦通过靶向 MAPK 信号通路抑制人胶质母细胞瘤的增殖、迁移和侵袭。

Multiflorane suppresses the proliferation, migration and invasion of human glioblastoma by targeting MAPK signalling pathway.

机构信息

Department of Neurosurgery, Shandong Provincial Hospital affiliated to Shandong University , Jinan , Shandong , China, 250021.

出版信息

J BUON. 2020 May-Jun;25(3):1631-1635.

PMID:32862615
Abstract

PURPOSE

Glioblastoma is one common malignant tumors of central nervous system and its treatment is limited by the unavailability of chemotherapeutic agents. This study was therefore undertaken to evaluate the anticancer effects of Multiflorane molecule against the U87 human glioblastoma cells and normal human astrocytes.

METHODS

The CCK8 assay was used to determine cell proliferation. Acridine orange (AO)/Ethidium bromide (EB) staining assays were used to detect apoptosis. Transwell assays were used to detect the cell migration and invasion. Western blotting was used to determine protein expression.

RESULTS

The results showed Multiflorane inhibited the proliferation of the human U87 cells with little effects on the normal cells. Investigation of the underlying mechanisms showed that Multiflorane induced apoptosis in U87 cells. Multiflorane-induced apoptosis was linked with upregulation of cleaved caspase-3, 8 and 9, as well as cleaved PARP. The Bax protein levels were increased and of Bcl-2 were decreased. Flow cytometric analysis showed that Multiflorane induced G2/M arrest of the U87 glioblastoma cells. Transwell assays showed that the molecule suppressed the migration and invasion of the U87 glioblastoma cells. Additionally, Multiflorane also blocked the phosphorylation of p38 MAPK1 dose-dependently.

CONCLUSION

Taken together, Multiflorane may prove beneficial in the treatment of glioblastoma.

摘要

目的

神经胶质瘤是一种常见的中枢神经系统恶性肿瘤,其治疗受到缺乏化疗药物的限制。因此,本研究旨在评估密蒙花素对 U87 人神经胶质瘤细胞和正常人星形胶质细胞的抗癌作用。

方法

CCK8 法测定细胞增殖。吖啶橙(AO)/溴化乙锭(EB)染色法检测细胞凋亡。Transwell 检测细胞迁移和侵袭。Western blot 检测蛋白表达。

结果

结果表明,密蒙花素抑制人 U87 细胞的增殖,对正常细胞影响较小。对潜在机制的研究表明,密蒙花素诱导 U87 细胞凋亡。密蒙花素诱导的凋亡与 cleaved caspase-3、8 和 9 以及 cleaved PARP 的上调有关。Bax 蛋白水平升高,Bcl-2 蛋白水平降低。流式细胞术分析表明,密蒙花素诱导 U87 神经胶质瘤细胞 G2/M 期阻滞。Transwell 检测表明该分子抑制 U87 神经胶质瘤细胞的迁移和侵袭。此外,密蒙花素还可剂量依赖性地阻断 p38 MAPK1 的磷酸化。

结论

综上所述,密蒙花素可能对神经胶质瘤的治疗有益。

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