萝卜硫素介导Akt/p70S6K信号传导诱导人鼻咽癌CNE-2细胞凋亡

doi:10.12092/j.issn.1009-2501.2019.07.010

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (7): 786-791.doi: 10.12092/j.issn.1009-2501.2019.07.010

萝卜硫素介导Akt/p70S6K信号传导诱导人鼻咽癌CNE-2细胞凋亡

赵丽，华夏，谭晔，胡承莲

恩施土家族苗族自治州中心医院急诊科，恩施 445000，湖北

收稿日期:2018-12-18 修回日期:2019-06-08 出版日期:2019-07-26 发布日期:2019-07-29
通讯作者: 胡承莲，女，本科，主治医师，主要研究鼻咽部疾病。 E-mail: hubei8888xx@163.com
作者简介:赵丽，女，本科，主治医师，主要研究肿瘤疾病的预防与治疗。 Tel: 18695050606 E-mail: 307312548@qq.com

Effects of sulforaphane-induced Akt/p70S6K signal transduction pathway on apoptosis of human nasopharyngeal cancer cells CNE-2

ZHAO Li, HUA Xia, TAN Ye, HU Chenglian

Department of Emergency, Central Hospital of En-shi Autonomous Prefecture, Enshi 445000, Hubei, China

Received:2018-12-18 Revised:2019-06-08 Online:2019-07-26 Published:2019-07-29

摘要/Abstract

摘要：

目的:研究萝卜硫素对人鼻咽癌CNE-2细胞增殖、凋亡的影响及其对Akt/p70S6K信号传导的作用。方法:采用CCK-8实验分析萝卜硫素对CNE-2细胞生长增殖的影响，流式细胞仪检测萝卜硫素对CNE-2细胞凋亡率及细胞周期分布的影响，Western blot技术检测CNE-2细胞中调控细胞周期的相关蛋白及Akt/p70S6K信号通路关键蛋白的表达水平。结果:采用萝卜硫素干预CNE-2细胞后，细胞增殖抑制率及凋亡率相对于对照组呈浓度依赖的方式显著增高，差异有统计学意义（P<0.05）；流式细胞仪分析提示，萝卜硫素干预能够将细胞停留在S期及G2/M期，并且萝卜硫素还能抑制细胞周期蛋白Cyclin A、Cyclin B、Cyclin D、Cyclin E以及CDK/p34的表达水平，与对照组相比差异有统计学意义（P<0.05）；此外，萝卜硫素还能抑制Akt/p70S6K信号通路关键蛋白p-Akt及p70S6K蛋白表达水平（P<0.05），但萝卜硫素与Akt激动剂IGF-I共同处理细胞后，上述蛋白表达量与对照组相比没有统计学差异（P>0.05）。结论:萝卜硫素可能通过干扰CNE-2细胞中Akt/p70S6K信号传导而发挥有效的抗增殖及促凋亡的作用。

关键词: 萝卜硫素, 人鼻咽癌细胞, 增殖, 凋亡, Akt/p70S6K信号通路

Abstract:

AIM: To study the effect of sulforaphane on the proliferation and apoptosis of CNE-2 cells, and to investigate the role of sulforaphane in the Akt/p70S6K signaling pathway. METHODS: CCK-8 test was used to detect cellular growth of CNE-2. Flow cytometry was carried out to observe apoptosis and cell cycle status. Expression levels of several cell cycle associated proteins and Akt/p70S6K pathway related proteins were determined by Western blot.RESULTS:Cell proliferation inhibitory rates and apoptotic rates of CNE-2 cells in various doses of sulforaphane groups were significantly increased as compared with control group with a dose-dependent manner (P<0.05). Flow cytometry results showed that sulforaphane arrestted NPC cells at the S-phases and G2/M-phases, and the expression levels of Cyclin A, Cyclin B, Cyclin D, Cyclin E and CDK/p34 were greatly decreased in sulforaphane group as compared with control group (P<0.05). Moreover, the expression levels of p-Akt and p70S6K in sulforaphane group were also decreased as compared with control group (P<0.05). However, the expression levels of these proteins above in sulforaphane+ IGF-I group unchanged as compared with control group (P>0.05). CONCLUSION: Sulforaphane exerts anti-proliferative and pro-apoptotic effects on CNE-2 cells through interfering with the Akt/p70S6K signaling pathways.

Key words: sulforaphane, human nasopharyngeal cancer cells, proliferation, apoptosis, Akt/p70S6K signaling pathways

中图分类号:

R739.6
R966

赵丽，华夏，谭晔，胡承莲. 萝卜硫素介导Akt/p70S6K信号传导诱导人鼻咽癌CNE-2细胞凋亡[J]. 中国临床药理学与治疗学, 2019, 24(7): 786-791.

ZHAO Li, HUA Xia, TAN Ye, HU Chenglian. Effects of sulforaphane-induced Akt/p70S6K signal transduction pathway on apoptosis of human nasopharyngeal cancer cells CNE-2[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 786-791.

参考文献

［1］Jin B, Dong P, Li K, et al. Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese［J］. Tumour Biol, 2014, 35(1): 345-349.
［2］Safavi A, Raad N, Raad N, et al. Epidemiology of nasopharyngeal cancers in Iran: Aa 6-year report ［J］. Asian Pac J Cancer Prev, 2015, 16(10): 4447-4450.
［3］Tortorella SM, Royce SG, Licciardi PV, et al. Dietary sulforaphane in cancer chemoprevention: the role of epigenetic regulation and HDAC inhibition ［J］. Antioxid Redox Signal, 2015, 22(16): 1382-1424.
［4］Nallasamy P, Si H, Babu PV, et al. Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway［J］. J Nutr Biochem, 2014, 25(8): 824-833.
［5］Li B, Kim DS, Yadav RK, et al. Sulforaphane prevents doxorubicin-induced oxidative stress and cell death in rat H9c2 cells［J］. Int J Mol Med, 2015, 36(1): 53-64.
［6］Park JH, Kim JW, Lee CM,et al. Sulforaphane inhibits the Th2 immune response in ovalbumin-induced asthma［J］. BMB Rep, 2012, 45(5): 311-316.
［7］Wu CC, Chuang HY, Lin CY, et al. Inhibition of Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells by dietary sulforaphane［J］. Mol Carcinog, 2013, 52(12): 946-958.
［8］Li X, Zhao Z, Li M, et al. Sulforaphane promotes apoptosis, and inhibits proliferation and self-renewal of nasopharyngeal cancer cells by targeting STAT signal through miRNA-124-3p［J］. Biomed Pharmacother, 2018, 103(12): 473-481.
［9］杨柳, 李昕. AKt /mTOR信号通路中p70S6K1、4E-BPs在促进肿瘤发生作用中的研究进展［J］. 现代肿瘤学, 2016, 24(5): 847-850.
［10］Wang W, Wen Q, Xu L, et al. Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma ［J］. PLoS One, 2014, 9(8): e106098.
［11］Wang L, Tian Z, Yang Q, et al. Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway ［J］. Oncotarget, 2015, 6(28): 25917-25931.
［12］Bauman JE, Zang Y, Sen M, et al. Prevention of carcinogen-induced oral cancer by sulforaphane ［J］. Cancer Prev Res (Phila), 2016, 9(7): 547-557.
［13］Agliarulo I, Matassa DS, Amoroso MR, et al. TRAP1 controls cell migration of cancer cells in metabolic stress conditions: Correlations with AKT/p70S6K pathways ［J］. Biochim Biophys Acta, 2015, 1853(10): 2570-2579.
［14］Sangawa A, Shintani M, Yamao N, et al. Phosphorylation status of Akt and caspase-9 in gastric and colorectal carcinomas［J］. Int J Clin Exp Pathol, 2014, 7(6): 3312-3317.
［15］Wu Q, Zhao QN, Song WD. The research and progress of PI3K/ Akt /mTOR signal transduction pathway in tumors ［J］. J Dis Control, 2013, 7(6): 346-347.
［16］Li GB, Shan CY, Liu L, et al. Tanshinone IIA inhibits HIF-1α and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6 /4E-BP1 signaling pathway［J］. PLoS One, 2015, 10(2): e0117440.
［17］Li X, Zhao Z, Li M, et al. Sulforaphane promotes apoptosis, and inhibits proliferation and self-renewal of nasopharyngeal cancer cells by targeting STAT signal through miRNA-124-3p［J］. Biomed Pharmacother, 2018, 103(8): 473-481.

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萝卜硫素介导Akt/p70S6K信号传导诱导人鼻咽癌CNE-2细胞凋亡

Effects of sulforaphane-induced Akt/p70S6K signal transduction pathway on apoptosis of human nasopharyngeal cancer cells CNE-2

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