10-羟基癸烯酸诱导肝癌细胞凋亡、周期阻滞及迁移抑制的机制

doi:10.7506/spkx1002-6630-20201022-226

食品科学 ›› 2021, Vol. 42 ›› Issue (23): 182-195.doi: 10.7506/spkx1002-6630-20201022-226

10-羟基癸烯酸诱导肝癌细胞凋亡、周期阻滞及迁移抑制的机制

臧延青，鞠雪莹，翟雨晴，姚笛，朱磊，王长远

（1.黑龙江八一农垦大学食品学院，黑龙江?大庆 163319；2.国家杂粮工程技术研究中心，黑龙江?大庆 163319）

出版日期:2021-12-15 发布日期:2021-12-29
基金资助:
“十三五”国家重点研发计划重点专项（SQ2018YFE020070）；黑龙江省自然科学基金项目（QC2017024）；黑龙江省青年创新人才培养项目（UNPYSCT-2017108）；黑龙江八一农垦大学研究生创新科研资助项目（YJSCX2019-Y51）

Mechanism by which 10-Hydroxy-2-decenoic Acid Induces Cell Apoptosis and Cycle Arrest and Inhibits Migration in Hepatocellular Carcinoma HepG2 Cells

ZANG Yanqing, JU Xueying, ZHAI Yuqing, YAO Di, ZHU Lei, WANG Changyuan

(1. College of Food Science, Heilongjiang Bayi Agricultural University, Daqing 163319, China; 2. National Coarse Cereals Engineering Research Center, Daqing 163319, China)

Online:2021-12-15 Published:2021-12-29

摘要/Abstract

摘要： 10-羟基癸烯酸（10-hydroxy-2-decenoic acid，10-HDA）是蜂王浆中特有的活性成分，本实验以肝癌HepG2细胞为研究对象，通过细胞毒性实验（cell counting kit-8，CCK-8）、Hoechst 33342/碘化丙啶（propidium iodide，PI）双染、流式细胞术及蛋白免疫印迹（Western blot）法分析10-HDA预处理后HepG2细胞凋亡的分子机制。结果发现，10-HDA对肝癌细胞系有明显的细胞毒性，对正常肝、肺、胃细胞（L-02、IMR-90、GES-1）无明显作用。同时，HepG2细胞经10-HDA处理后，Bcl-2表达水平下调、Bax表达水平上调，触发了线粒体凋亡途径，线粒体膜电位下降，从而导致细胞色素c（cytochrome c，Cyt c）得到释放，Caspase-3被活化，最终线粒体依赖性凋亡。此外，10-HDA能够诱导活性氧（reactive oxygen species，ROS）累积，激活了丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）和信号转导与转录活化因子（signal transducer and activator of transcription，STAT）3信号通路，促进P-Jun氨基末端激酶（jun N-terminal kinase，JNK）、P-P38表达，抑制P-细胞外调节蛋白激酶（extracellular-signal-regulated kinase，ERK）、P-STAT3表达，进而调控细胞周期相关蛋白，使细胞周期阻滞在G2/M期。最后，10-HDA通过激活转化生长因子-β1（transforming growth factor-β1，TGF-β1）信号通路，验证了其抑制迁移作用。综上所述，10-HDA通过累积ROS、激活MAPK和STAT3信号通路，诱导细胞凋亡。

关键词: 10-羟基癸烯酸；肝癌细胞；细胞凋亡；周期阻滞；细胞迁移；信号通路

Abstract: 10-Hydroxy-2-decenoic acid (10-HDA) is a unique bioactive component of royal jelly. In this study, the molecular mechanism of apoptosis in HepG2 cells induced by 10-HDA was analyzed by cell counting kit-8 (CCK-8) assay, Hoechst 33342/propidium iodide (PI) staining, flow cytometry and Western blot. The results showed that 10-HDA had significant cytotoxicity on liver cancer cell lines but not normal cells (L-02, IMR-90 or GES-1). 10-HDA down-regulated the expression of Bcl-2, up-regulated the expression of Bax , triggered the mitochondrial apoptosis pathway, and decreased mitochondrial membrane potential, thus leading to the release of cytochrom c (Cyt c), the activation of caspase-3, and eventually mitochondria-dependent apoptosis. In addition, 10-HDA induced reactive oxygen species (ROS) accumulation, activated the mitogen-activated protein kinase (MAPK) signaling pathway and the signal transducer and activator of transcription 3 (STAT3) signaling pathway, promoted the expression of jun N-terminal kinase (JNK) and P-P38, and inhibited the expression of extracellular-signal-regulated kinase (ERK) and P-STAT3, consequently regulating the expression of cell cycle related-proteins to arrest the cell cycle at the G2/M phase. Finally, 10-HDA was demonstrated to inhibit cancer cell migration by activating the transforming growth factor-β1 (TGF-β1) signaling pathway. In conclusion, 10-HDA can induce cell apoptosis by causing ROS accumulation and activating the MAPK and STAT3 signaling pathways.

Key words: 10-hydroxy-2-decenoic acid; hepatocellular carcinoma cells; cell apoptosis; cycle arrest; cell migration; signaling pathway

中图分类号:

R735.7

臧延青，鞠雪莹，翟雨晴，姚笛，朱磊，王长远. 10-羟基癸烯酸诱导肝癌细胞凋亡、周期阻滞及迁移抑制的机制[J]. 食品科学, 2021, 42(23): 182-195.

ZANG Yanqing, JU Xueying, ZHAI Yuqing, YAO Di, ZHU Lei, WANG Changyuan. Mechanism by which 10-Hydroxy-2-decenoic Acid Induces Cell Apoptosis and Cycle Arrest and Inhibits Migration in Hepatocellular Carcinoma HepG2 Cells[J]. FOOD SCIENCE, 2021, 42(23): 182-195.

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10-羟基癸烯酸诱导肝癌细胞凋亡、周期阻滞及迁移抑制的机制

Mechanism by which 10-Hydroxy-2-decenoic Acid Induces Cell Apoptosis and Cycle Arrest and Inhibits Migration in Hepatocellular Carcinoma HepG2 Cells

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