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木犀草素对表皮生长因子诱导的人乳腺癌细胞增殖的抑制作用及其机制

隋佳琪, 谢鲲鹏, 谢明杰^*

辽宁师范大学生命科学学院，辽宁省生物技术与分子药物研发重点实验室，大连 116081

摘要

本研究的目的是探讨木犀草素体外抑制表皮生长因子(epidermal growth factor, EGF)诱导的乳腺癌细胞增殖的机制。MTT法检测了木犀草素对乳腺癌细胞MCF-7和MDA-MB-231增殖的影响以及木犀草素对EGF诱导的乳腺癌细胞MCF-7增殖的影响。Western blot法检测了木犀草素对EGF受体、磷脂酰肌醇3蛋白激酶(PI3K)/Akt、丝裂原活化蛋白激酶(MAPK)/Erk1/2及转录活化因子3 (STAT3)蛋白表达的影响。结果显示，木犀草素能显著抑制乳腺癌细胞MCF-7和MDA-MB-231的增殖，但对MCF-7细胞的影响更显著，因此本文后续实验以MCF-7为研究对象。进一步研究结果显示，木犀草素对EGF诱导的MCF-7细胞增殖也有显著的抑制作用，Western blot结果表明，木犀草素和EGFR通路阻断剂AG1478均能抑制EGF诱导的EGF受体和STAT3蛋白磷酸化水平，木犀草素、Akt通路抑制剂LY294002以及Erk1/2通路阻断剂PD98059均能显著抑制EGF诱导的Akt和Erk1/2蛋白磷酸化水。以上结果揭示，木犀草素能抑制人乳腺癌细胞EGF信号通路，其中PI3K/Akt、MAPK/Erk1/2、STAT3信号通路是其发挥作用的主要下游信号转导通路。本实验结果为将木犀草素开发成新型抗乳腺癌药物提供了理论依据。

关键词： 乳腺癌; 木犀草素 ; 表皮生长因子受体 ; Akt ; MAPK ; STAT3

分类号：R736.3

Inhibitory effect of luteolin on the proliferation of human breast cancer cell lines induced by epidermal growth factor

SUI Jia-Qi, XIE Kun-Peng, XIE Ming-Jie^*

School of Life Science, Liaoning Normal University, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Dalian 116081, China

Abstract

The aim of the present study was to investigate the mechanism of the inhibitory effect of luteolin on the proliferation of breast cancer cells induced by epidermal growth factor (EGF) in vitro. MTT assay was used to detect the inhibitory effect of luteolin on the proliferation of MCF-7 and MDA-MB-231 cells as well as the effect on the proliferation of MCF-7 cells induced by EGF. Western blotting was used to detect the effects of luteolin on the expression of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (Erk) 1/2 and signal transducers and activators of transcription-3 (STAT3) in MCF-7 cells induced by EGF. The results showed that luteolin could significantly inhibit the proliferation of MCF-7 and MDA-MB-231 cells, and the inhibitory effect on MCF-7 cells was more prominent. Moreover, luteolin could inhibit the proliferation of MCF-7 cells induced by EGF. Western blotting results showed that luteolin and AG1478 (an inhibitor of EGFR signaling) could inhibit the expression of p-EGFR and p-STAT3 in MCF-7 cells induced by EGF. Luteolin, LY294002 (an inhibitor of Akt signaling) and PD98059 (an inhibitor of Erk1/2 signaling) could inhibit the expression of p-Akt and p-Erk1/2 respectively in MCF-7 cells induced by EGF. Our data suggest that luteolin may inhibit EGF-induced activities of EGFR signaling pathway in human breast cancer cell lines, and PI3K/Akt, MAPK/Erk1/2, STAT3 signal pathways may be the major pathways that mediate the inhibitory effect of luteolin on EGFR signaling. Overall, our results may provide a theoretical foundation for the development of luteolin as anti-tumor drug.

Key words: breast cancer; luteolin ; epidermal growth factor receptor ; Akt ; MAPK ; STAT3

收稿日期：2015-10-08　　录用日期：2015-12-10

通讯作者：谢明杰　　E-mail:

引用本文：

隋佳琪, 谢鲲鹏, 谢明杰. 木犀草素对表皮生长因子诱导的人乳腺癌细胞增殖的抑制作用及其机制[J]. 生理学报 2016; 68 (1): 27-34.

SUI Jia-Qi, XIE Kun-Peng, XIE Ming-Jie. Inhibitory effect of luteolin on the proliferation of human breast cancer cell lines induced by epidermal growth factor. Acta Physiol Sin 2016; 68 (1): 27-34