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甘薯酮III通过抑制上皮-间质转化和FAK-AKT信号通路抑制人肺癌细胞迁移。

Batatasin III Inhibits Migration of Human Lung Cancer Cells by Suppressing Epithelial to Mesenchymal Transition and FAK-AKT Signals.

作者信息

Pinkhien Tatchakorn, Petpiroon Nareerat, Sritularak Boonchoo, Chanvorachote Pithi

机构信息

Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

出版信息

Anticancer Res. 2017 Nov;37(11):6281-6289. doi: 10.21873/anticanres.12079.

Abstract

BACKGROUND/AIM: Lung cancer is the leading cause of cancer-related deaths worldwide. Compound Batatasin III isolated from Dendrobium draconis Rchb.f. was tested for the possible anti-cancer activities including anti-proliferative, anti-migration and invasion in human non-small lung cancer H460 cells.

MATERIALS AND METHODS

The effect of Batatasin III on viability and proliferation of H460 cells was investigated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyl tetrazoliumbromide (MTT) assay. Migration and invasion assays were performed. Filopodia formation was determined by phalloidin-rhodamine staining. The hallmark signaling proteins in regulation of epithelial to mesenchymal transition (EMT), proliferation, and migration were determined by western blot analysis.

RESULTS

Batatasin III at concentrations lower than 100 μM has no cytotoxic effects. The compound at 25-100 μM exhibited anti-proliferative activity at 48 h after treatment. Regarding cell motility, Batatasin III decreased migration and invasion of cells. Filopodia were found to be significantly reduced in Batatasin III treated cells. These effects correlated with the results from western blot analysis showing that the phosphorylation of focal adhesion kinase on Try397 (p-FAK (Try397)), the active protein kinase B (AKT), and cell division cycle 42 (CDC42) were significantly reduced. Besides, Batatasin III significantly suppressed EMT indicated by the decrease of N-cadherin and Vimentin, and up-regulation of E-cadherin.

CONCLUSION

Batatasin III has anti-cancer activities; inhibits cancer migration and invasion by suppressing EMT. Our findings establish Batatasin III as a potential compound for further studies aimed at finding a better, more effective treatment approach for lung cancer.

摘要

背景/目的:肺癌是全球癌症相关死亡的主要原因。对从石斛中分离出的化合物Batatasin III进行了测试,以研究其在人非小细胞肺癌H460细胞中可能的抗癌活性,包括抗增殖、抗迁移和抗侵袭活性。

材料与方法

采用3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐(MTT)法研究Batatasin III对H460细胞活力和增殖的影响。进行了迁移和侵袭实验。通过鬼笔环肽-罗丹明染色确定丝状伪足的形成。通过蛋白质免疫印迹分析确定上皮-间质转化(EMT)、增殖和迁移调节中的标志性信号蛋白。

结果

浓度低于100μM的Batatasin III没有细胞毒性作用。该化合物在25-100μM浓度下处理48小时后表现出抗增殖活性。关于细胞运动性,Batatasin III降低了细胞的迁移和侵袭能力。在经Batatasin III处理的细胞中发现丝状伪足明显减少。这些效应与蛋白质免疫印迹分析结果相关,该分析表明粘着斑激酶在Try397位点的磷酸化(p-FAK(Try397))、活性蛋白激酶B(AKT)和细胞分裂周期42(CDC42)显著降低。此外,Batatasin III通过降低N-钙粘蛋白和波形蛋白并上调E-钙粘蛋白,显著抑制了EMT。

结论

Batatasin III具有抗癌活性;通过抑制EMT抑制癌症迁移和侵袭。我们的研究结果表明Batatasin III是一种有潜力的化合物,可用于进一步研究,以寻找更好、更有效的肺癌治疗方法。

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