Eupatilin inhibits glioma proliferation, migration, and invasion by arresting cell cycle at G1/S phase and disrupting the cytoskeletal structure
Eupatilin inhibits glioma proliferation, migration, and invasion by arresting cell cycle at G1/S phase and disrupting the cytoskeletal structure
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DOI：
10.2147/cmar.s207257
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Xu, Ruxiang
中科院分区：
文献类型：
--
作者：
Fei, Xiaowei;Wang, Ji;Xu, Ruxiang
目的：杜仲苷是从菊科植物艾叶中提取的一种黄酮类化合物，具有抗肿瘤作用。脑胶质瘤是颅内最常见的恶性肿瘤，死亡率高，术后预后差。关于欧帕替林对脑胶质瘤治疗作用的研究较少。方法：采用Cell Counting Kit-8法检测eupatilin对胶质瘤细胞增殖和存活的影响。细胞迁移分析与划痕伤口愈合试验和侵袭分析transwell assays.Results：我们发现，eupatilin显着抑制胶质瘤细胞的活力和增殖，通过阻滞在G1/S期的细胞周期。此外，eupatilin破坏细胞骨架的结构，并通过“P-LIMK”/cofilin途径影响F-肌动蛋白解聚，从而抑制胶质瘤的迁移。我们还发现，eupatilin抑制胶质瘤的侵袭。其机制可能与上皮-间充质转化的破坏有关，eupatilin还影响RECK/基质金属蛋白酶途径。但是，我们没有观察到eupatilin对胶质瘤的促凋亡作用，这与其他研究不一致。结论：Eupatilin能抑制胶质瘤细胞的存活和增殖，减弱其迁移和侵袭能力，抑制肿瘤生长，但不促进细胞凋亡。因此，由于药物治疗脑胶质瘤临床疗效差，耐药率高，因此，欧帕替林的出现为脑胶质瘤患者带来了新的曙光。
Purpose: Eupatilin is a pharmacologically active flavonoid extracted from Asteraceae argyi that has been identified as having antitumor effects. Gliomas are the most common intracranial malignant tumors and are associated with high mortality and a poor postoperative prognosis. There are few studies on the therapeutic effects of eupatilin on glioma. Therefore, we explored the efficacy and the underlying molecular mechanism of eupatilin on glioma.Methods: The effect of eupatilin on cell proliferation and viability was detected using Cell Counting Kit-8 assays. Cell migration was analyzed with a scratch wound healing assay and invasion was analyzed using transwell assays.Results: We found that eupatilin significantly inhibits the viability and proliferation of glioma cells by arresting the cell cycle at the G1/S phase. In addition, eupatilin disrupts the structure of the cytoskeleton and affects F-actin depolymerization via the "P-LIMK"/cofilin pathway, thereby inhibiting the migration of glioma. We also found that eupatilin inhibits the invasion of gliomas. The underlying mechanism may be related to the destruction of epithelial-mesenchymal transition, with eupatilin also affecting the RECK/matrix metal-loproteinase pathway. However, we did not observe the proapoptotic effect of eupatilin on glioma, which is inconsistent with other studies. Finally, we observed a significant inhibitory effect of eupatilin on U87MG glioma in xenograft nude mice.Conclusion: Eupatilin inhibits the viability and proliferation of glioma cells, attenuates the migration and invasion, and inhibits tumor growth in vivo, but does not promote apoptosis. Therefore, due to the poor clinical efficacy of drug treatment of glioma and high drug resistance, the emergence of eupatilin brings a new dawn for glioma patients.