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葶苈子通过上调 microRNA-195 发挥抑制人肺癌发展的抗肿瘤功能。

Ailanthone exerts an antitumor function on the development of human lung cancer by upregulating microRNA-195.

机构信息

Department of Thoracic Surgery, Linyi Central Hospital, Linyi, China.

出版信息

J Cell Biochem. 2019 Jun;120(6):10444-10451. doi: 10.1002/jcb.28329. Epub 2018 Dec 19.

Abstract

BACKGROUND

Lung cancer is a common leading cause of cancer-related death worldwide. Ailanthone, a natural compound isolated from Chinese herb Ailanthus altissima, has been reported to exert antiproliferative effects on various cancer cells.

METHODS

The present study aimed to investigate the role of ailanthone in the lung cancer cells and the correlation between the ailanthone and microRNA (miR)-195. The cell viability, proliferation, and apoptosis were determined by cell counting kit-8 assay, bromodeoxyuridine incorporation method, annexin V-fluorescein isothiocyanate/propidium iodide assay, respectively. Apoptosis- and autophagy-related proteins, as well as regulatory factors in the signaling pathways, were analyzed by Western blot method. The expression of miR-195 was quantified by quantitative reverse transcription-polymerase chain reaction.

RESULTS

The results confirmed that ailanthone was involved in the lung cancer cell progress by inhibiting cell viability and proliferation, but promoted cell apoptosis and autophagy. We also found that ailanthone upregulated the expression of miR-195. Further, the downregulated miR-195 inhibited the apoptosis and autophagy induced by ailanthone. Moreover, our studies revealed that miR-195 inhibitor promoted the phosphorylation of PI3K, AKT, JAK, and STAT3, which was inhibited by ailanthone.

CONCLUSION

All these findings suggest that ailanthone plays key roles in lung cancer progress and is closely correlated with miR-195 expression.

摘要

背景

肺癌是全球癌症相关死亡的常见主要原因。从中国草药樗树中分离得到的天然化合物苦木内酯已被报道对各种癌细胞具有抗增殖作用。

方法

本研究旨在探讨苦木内酯在肺癌细胞中的作用,以及苦木内酯与 microRNA(miR)-195 之间的相关性。通过细胞计数试剂盒-8 测定法、溴脱氧尿苷掺入法、 Annexin V-荧光素异硫氰酸酯/碘化丙啶法分别测定细胞活力、增殖和细胞凋亡。通过 Western blot 法分析凋亡和自噬相关蛋白以及信号通路中的调节因子。通过定量逆转录聚合酶链反应定量 miR-195 的表达。

结果

结果证实,苦木内酯通过抑制细胞活力和增殖参与肺癌细胞的进展,但促进细胞凋亡和自噬。我们还发现苦木内酯上调了 miR-195 的表达。进一步的,下调 miR-195 抑制了苦木内酯诱导的细胞凋亡和自噬。此外,我们的研究表明,miR-195 抑制剂促进了 PI3K、AKT、JAK 和 STAT3 的磷酸化,而这一过程被苦木内酯所抑制。

结论

所有这些发现表明,苦木内酯在肺癌进展中发挥关键作用,与 miR-195 表达密切相关。

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