MAPK/ERK信号通路在益气解毒方水提物诱导鼻咽癌细胞凋亡中的作用  

Role of MAPK/ERK signaling pathway in apoptosis of nasopharyngeal carcinoma cells by Yiqi Jiedu formula

作　　者：胡晶[1,2,5] 刘洁 徐冰雁[1,2] 戴娜 胡梅[3] 周芳亮[3,4] 史红健[2,4] 罗晶婧[2,3] 蔺婷 何迎春[2,3,4] HU Jing;LIU Jie;XU Bing-yan;DAI Na;HU Mei;ZHOU Fang-liang;SHI Hong-jian;LUO Jing-jing;LIN Ting;HE Ying-chun(Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China;Hunan Provincial Key Lab for the Prevention and Treatment of Ophthalmology andOtolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;College of Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;Hunan Provincial ResearchEngineering Technology Center for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases withTraditional Chinese Medicine and Visual Function Protection, Hunan University of Chinese Medicine, Changsha 410208, China;College of traditional Chinese Medicine, Changsha Medical University, Changsha 410219,China)

机构地区：[1]湖南中医药大学研究生学院,湖南长沙410208 [2]湖南中医药大学中医药防治眼耳鼻咽喉疾病湖南省重点实验室,湖南长沙410208 [3]湖南中医药大学医学院,湖南长沙410208 [4]湖南中医药大学湖南省中医药防治眼耳鼻咽喉疾病与视功能保护工程技术研究中心,湖南长沙410208 [5]长沙医学院中医学院,湖南长沙410219

出　　处：《中国药理学通报》2019年第11期1613-1621,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81573721,81874408);湖南省自然科学基金资助项目(No 2016JJ6117,2017JJ3246);湖南中医药大学研究生创新项目(No 2017CX33)

摘　　要：目的 研究益气解毒方水提物对鼻咽癌细胞凋亡的影响,并从MAPK/ERK信号通路探讨其诱导凋亡的作用机制。方法 CCK-8法检测益气解毒方水提物对CNE1、CNE2细胞增殖的影响;Hoechst 33342染色法、JC-10染色法、荧光双染流式细胞仪检测其对CNE1、CNE2细胞凋亡的影响;Western blot法检测其对CNE1、CNE2细胞蛋白表达的影响。结果 益气解毒方水提物能抑制CNE1、CNE2细胞增殖( P <0.05)、诱导凋亡( P <0.05);药物作用48 h后,Survivin、XIAP、Bcl-2表达下降,Bax表达上升,MAPK/ERK信号通路关键蛋白p-c-Raf、p-MEK、p-ERK表达下降( P <0.05);在此基础上,加入激活剂ISO和益气解毒方水提物后,与单用益气解毒方水提物相比,p-c-Raf、p-MEK、p-ERK1/2表达上调,Survivin、XIAP、Bcl-2表达增加,Bax表达下降,促凋亡效应也降低( P <0.05)。结论 益气解毒方水提物可诱导鼻咽癌细胞凋亡,该效应与其抑制MAPK/ERK信号通路关键蛋白p-c-Raf、p-MEK、p-ERK1/2表达,进而下调Survivin、XIAP、Bcl-2表达,上调Bax表达有关。Aim To study the effect of Yiqi Jiedu formula extract on the apoptosis of nasopharyngeal carcinoma cells, and explore the mechanism of its induction of apoptosis from MAPK/ERK signaling pathway. Methods The effect of Yiqi Jiedu Formula extract on the proliferation of CNE1 and CNE2 cells was detected by CCK-8. The apoptosis of CNE1 and CNE2 cells was detected by Hoechst 33342 staining, JC-10 staining and fluorescence double dye flow cytometer staining. The protein expression of CNE1 and CNE2 cells was detected by Western blot. Results Yiqi Jiedu formula extract inhibited the proliferation ( P <0.05) and induced apoptosis ( P <0.05) of CNE1 and CNE2 cells. After 48 h of drug treatment, the expression of Survivin, XIAP and Bcl-2 decreased, Bax increased, and p-c-Raf, p-MEK and p-ERK1/2 of MAPK/ERK signaling pathway significantly decreased ( P <0.05). On this basis, after adding activator of MAPK/ERK signaling pathway ISO, the expression of p-c-Raf, p-MEK and p-ERK1/2,Survivin, XIAP and Bcl-2 increased, while the expression of Bax decreased compared with the extract of YQ group. Drug-induced apoptosis effects were also reduced. Conclusions Yiqi Jiedu formula extract can induce the apoptosis of nasopharyngeal carcinoma cells, which inhibits the expression of key proteins p-c-Raf, p-MEK and p-ERK1/2 in MAPK/ERK signaling pathway, and then down-regulates the expression of Survivin, XIAP, Bcl-2 and up-regulates the expression of Bax.

关 键 词：益气解毒方 鼻咽癌 细胞凋亡 MAPK/ERK信号通路 Survivin XIAP 

分 类 号：R289.5[医药卫生—方剂学] R329.24[医药卫生—中药学]