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印防己毒素内酯通过调节凋亡相关蛋白的表达、G2/M期细胞周期阻滞以及抑制JAK/STAT信号通路来抑制人肺癌生长。

Linderalactone inhibits human lung cancer growth by modulating the expression of apoptosis-related proteins, G2/M cell cycle arrest and inhibition of JAK/STAT signalling pathway.

作者信息

Deng Yanglin, Li Ya

机构信息

Department of Pharmacy, the First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , China , 650032.

出版信息

J BUON. 2019 Mar-Apr;24(2):566-571.

Abstract

PURPOSE

The main purpose of the current research work was to evaluate the antitumor effects of linderalactone in A-549 human lung carcinoma cell line along with the study its effects on apoptosis-related proteins, cell cycle phase distribution and JAK/STAT signalling pathway.

METHODS

The viability of lung cancer cell line was investigated by MTT assay at varying doses of linderalactone. Apoptosis was detected by using fluorescence microscopy and flow cytometry. Cell cycle analysis was carried out by flow cytometery. The protein expression was examined by western blotting.

RESULTS

Linderalactone could inhibit the proliferation of the lung cancer A-549 cells with an IC50 of 15 µM. Further investigations indicated the antiproliferative effects of linderalactone are due to apoptosis induction which was further confirmed by Bax and Bcl-2 expression. It also induced G2/M cell cycle arrest which was also associated with alteration of the expression of several important proteins. Furthermore, linderalactone could also suppress the JAK/STAT signalling pathway.

CONCLUSIONS

In conclusion, linderalactone could be developed as a potential drug candidate against lung cancer provided that further in depth studies are carried out in this direction focusing on its in vivo efficacy.

摘要

目的

当前研究工作的主要目的是评估乌药内酯对A-549人肺癌细胞系的抗肿瘤作用,并研究其对凋亡相关蛋白、细胞周期阶段分布和JAK/STAT信号通路的影响。

方法

采用MTT法检测不同剂量乌药内酯对肺癌细胞系活力的影响。通过荧光显微镜和流式细胞术检测细胞凋亡。采用流式细胞术进行细胞周期分析。通过蛋白质印迹法检测蛋白质表达。

结果

乌药内酯能够抑制肺癌A-549细胞的增殖,IC50为15 μM。进一步研究表明,乌药内酯的抗增殖作用归因于诱导细胞凋亡,这通过Bax和Bcl-2表达得到进一步证实。它还诱导G2/M期细胞周期阻滞,这也与几种重要蛋白质表达的改变有关。此外,乌药内酯还可以抑制JAK/STAT信号通路。

结论

总之,如果在此方向上针对其体内疗效进行进一步深入研究,乌药内酯有望开发成为一种潜在的抗肺癌药物候选物。

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