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去乙酰异缬草素破坏微管动力学并在体外导致人胃癌细胞的G/M期阻滞。

Deacetylisovaltratum disrupts microtubule dynamics and causes G/M-phase arrest in human gastric cancer cells in vitro.

作者信息

Zhang Dan, Zhang Bo, Zhou Li-Xin, Zhao Jun, Yan You-You, Li Yang-Ling, Zeng Jian-Mei, Wang Lin-Ling, Yang Bo, Lin Neng-Ming

机构信息

Laboratory of Clinical Pharmacology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.

Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou 310006, China.

出版信息

Acta Pharmacol Sin. 2016 Dec;37(12):1597-1605. doi: 10.1038/aps.2016.91. Epub 2016 Sep 26.

Abstract

AIM

Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms.

METHODS

Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process.

RESULTS

DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC values of 12.0 and 28.8 μmol/L, respectively, at 24 h of treatment. Treatment with DI (10-100 μmol/L) dose-dependently promoted tubulin polymerization, and induced significant G/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells.

CONCLUSION

DI induces G/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.

摘要

目的

去乙酰异缬草素(DI)是从传统中药白花败酱中分离得到的,具有抗癌活性。在此,我们研究了DI对人胃癌细胞系的体外作用,并阐明其抗癌机制。

方法

用DI处理人胃癌AGS和HGC-27细胞系,采用MTT法检测细胞活力。使用流式细胞术检测细胞周期阶段、凋亡和线粒体膜电位。通过蛋白质印迹法分析蛋白质水平。采用微管蛋白聚合试验和免疫荧光法表征微管蛋白聚合过程。

结果

DI以剂量和时间依赖性方式抑制AGS和HGC-27细胞的活力,在处理24小时时,其IC值分别为12.0和28.8μmol/L。用DI(10 - 100μmol/L)处理剂量依赖性地促进微管蛋白聚合,并在AGS和HGC-27细胞中诱导显著的G/M期细胞周期阻滞。此外,DI处理破坏了线粒体膜电位,并在AGS和HGC-27细胞中诱导了半胱天冬酶依赖性凋亡。

结论

DI通过破坏人胃癌细胞中的微管蛋白聚合诱导G/M期阻滞,这突出了其强大的抗癌活性以及在胃癌治疗中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f04/5260834/0c33b1c34be6/aps201691f1.jpg

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