PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展

刘陆; 高小玲; 李墨颜; 刘雪宁; 陈玉龙; 崔姗姗

doi:10.13422/j.cnki.syfjx.20201502

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PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展

综述 | 更新时间：2020-09-09

- PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展
- Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine
- 中国实验方剂学杂志 2020年26卷第14期页码：217-224
- 作者机构：
  
  河南中医药大学，郑州 450046
- 作者简介：
  
  刘陆，在读硕士，从事中西医结合基础研究，E-mail：993517556@qq.com
  崔姗姗，教授，硕士生导师，从事肿瘤病因病机与防治研究，E-mail：sscui13@163.com
- 基金信息：
  
  国家自然科学基金青年基金项目(81803981);河南省高等学校青年骨干教师项目(2018GGJS084);河南省科技厅项目(182102310320)
- DOI：10.13422/j.cnki.syfjx.20201502
  中图分类号： R2-0;R22;R285.5;R284
- 纸质出版日期：2020-07-20，
  
  网络出版日期：2020-05-08，
- 稿件说明：
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刘陆,高小玲,李墨颜等.PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展[J].中国实验方剂学杂志,2020,26(14):217-224.

LIU Lu,GAO Xiao-ling,LI Mo-yan,et al.Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):217-224.
刘陆,高小玲,李墨颜等.PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展[J].中国实验方剂学杂志,2020,26(14):217-224. DOI： 10.13422/j.cnki.syfjx.20201502.

LIU Lu,GAO Xiao-ling,LI Mo-yan,et al.Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):217-224. DOI： 10.13422/j.cnki.syfjx.20201502.

摘要

食管癌是我国肿瘤发病死亡率较高的恶性肿瘤之一，国家癌症中心2019年发布的中国最新癌症报告中显示，2015年食管癌患病人口达到了24.6万人，死亡人数高达18.8万人。如何有效的治疗食管癌，提高患者的生存率也是当今医学领域中亟待解决的首要问题之一。磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路是调节机体内细胞存活、分化及凋亡的重要信号通路之一，在各种癌症的发生及作用机制中起到了重要的作用。近年来的研究表明，PI3K/Akt信号通路的激活是调节食管癌细胞的增殖、凋亡、周期阻滞、迁移与侵袭的重要因素。长期的临床观察发现中药治疗食管癌作用平稳、毒副作用小，尤其在改善肿瘤患者的生活质量，延长患者生存期等方面作用独特、效果显著。用中药干预该信号通路以探索其对食管癌的作用机制是目前中药治疗食管癌的研究热点。本文对2009—2019年CNKI，Pubmed数据库中PI3K/Akt信号通路，食管癌，miRNA为关键词进行检索，共检索文献226篇，整理、归纳与中药，食管癌，miRNA，PI3K/Akt信号通路相关文献61篇。综述了PI3K/Akt信号通路在食管癌中的作用机制，miRNA与PI3K/Akt 信号通路与食管癌发生发展的关系以及中药如何通过调控PI3K/Akt信号通路中相关蛋白的表达而抑制细胞增殖、影响细胞生长周期、诱导细胞凋亡、诱导细胞自噬、抑制肿瘤的侵袭和转移、抑制血管生成等，最终对食管癌起到一定的改善作用。对中医药治疗食管癌提供理论基础以及科学依据。

Abstract

Esophageal cancer is one of the malignant tumors with a high morbidity and mortality in China. According to China's latest cancer report released by the National Cancer Center in 2019

the number of people suffering from esophageal cancer reached 246 000 in 2015

and the death toll reached 188 000. How to effectively treat esophageal cancer and improve the survival rate of patients is one of the most urgent problems in the field of medicine. Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most important signaling pathway for regulating cell survival

differentiation and apoptosis in the body. It also plays an important role in the occurrence and mechanism of various cancers. Recent studies have shown that the activation of PI3K/Akt signaling pathway is an important factor in regulating proliferation

apoptosis

cycle arrest

migration and invasion of esophageal cancer cells. The long-term clinical observation found that traditional Chinese medicine has a stable effect in the treatment of esophageal cancer and little side effects

especially in improving the quality of life of cancer patients and prolonging the survival period of patients. At present

it is a research hotspot to intervene this signal pathway with traditional Chinese medicine in the treatment of esophageal cancer

so as to explore its mechanism of action on esophageal cancer. This paper focused on literatures in CNKI and PubMed databases from 2009 to 2019

with PI3K/Akt signaling pathway

esophageal cancer and miRNA as the key words. A total of 226 literatures were retrieved

and 61 literatures relating to traditional Chinese medicine

esophageal cancer

miRNA and PI3K/Akt signaling pathway were sorted out and summarized. This paper reviewed the mechanism of PI3K/Akt signaling pathway in esophageal cancer

the relationship between miRNA and PI3K/Akt signaling pathway and esophageal cancer

and how traditional Chinese medicine can regulate the expressions of relevant proteins in PI3K/Akt signaling pathway to inhibit cell proliferation

affect cell growth cycle

induce cell apoptosis

inducing cell autophagy

inhibit tumor invasion and metastasis

inhibit angiogenesis. Finally

it can improve esophageal cancer to provide theoretical basis and scientific basis for the treatment of esophageal cancer with traditional Chinese medicine.

关键词

食管癌磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路miRNA中药

Keywords

esophageal cancerphosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathwaymiRNAtraditional Chinese medicine

references

JIA S,LI H,ZENG H,et al.Association of cancer prevention awareness with esophageal cancer screening participation rates:results from a population-based cancer screening program in rural China[J].Chin J Res,2019,31(4):601-608.

张思维,张敏,李光琳,等.2003～2007年中国食管癌发病与死亡分析[J].中国肿瘤,2012,21(4):241-247.

白俊,吴也可,吴克明,等.雷公藤甲素通过PI3K/AKT/mOR通路诱导卵巢颗粒细胞自噬的实验研究[J].中国中药杂志,2019,44(16):3429-3434.

MARKOWSKA A,PAWALOWSKA M,LUBIN J,et al.Signalling pathways in endometrial cancer[J].Contemp Oncol (Pozn),2014,18(3):143-148.

倪琛琛,于敏,张志红.EGFR与PI3K/AKT信号通路相关蛋白在非小细胞肺癌组织中的表达及其意义[J].安徽医科大学学报,2011,46(12):1264-1266.

BECK J T,ISMAIL A,TOLOMEO C.Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway:an emerging treatment strategy for squamous cell lung carcinoma[J].Cancer Treat Rev,2014,40(8):980-989.

涂志军,胡高云,李乾斌.p70核糖体蛋白S6激酶抑制剂的研究进展[J].药学学报,2015,50(3):261-271.

ZHAO H,YANG J,FAN T,et al.RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway[J].Tumour Biol,2012,33(5):1363-1374.

张小三,张一鸣,赵燕,PI3K/AKT信号通路相关蛋白表达与食管癌淋巴结转移的关系[J].癌症进展,2019,17(4):460-463.

SHI N,YU H,CHEN T.Inhibition of esophageal cancer growth through the suppression of PI3K/Akt/mTOR signaling pathway[J].Onco Targets Ther,2019,17(12):7637-7647.

ZHENG T L,LI D P,HE Z F,et al.miR-145 sensitizes esophageal squamous cell carcinoma to cisplatin through directly inhibiting PI3K/Akt signaling pathway[J].Cancer Cell Int,2019,19(1):250.

尚观胜,秦艺玮,梁卫东,等,PI3K/Akt抑制剂对人食管癌EC109细胞的生长抑制及促凋亡作用研究[J].重庆医学,2013r,42(16):1841-1843.

WU N,ZHU Y,XU X,et al.The anti-tumor effects of dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A on inducing autophagy in esophageal squamous cell carcinoma[J].J Cancer,2018,9(6):987-997.

CHANDRA S,VIMAL D,SHARMA D,et al.Role of miRNAs in development and disease:lessons learnt from small organisms[J].Life Sci,2017,15;185:8-14.

PETROVIC N,ERGUN S.miRNAs as potential treatment targets and treatment options in cancer[J].Mol Diagn Ther,2018,22(2):157-168.

吴耀松,陈玉龙,尹素改,等,结合基因芯片表达谱研究miRNAs在食管鳞癌中的作用[J].世界华人消化杂志,2011.19(36):3687-3691.

YANG Q S,JIANG L P,HE C Y,et al.Up-regulation of microRNA-133a inhibits the MEK/ERK signaling pathway to promote cell apoptosis and enhance radio-sensitivity by targeting egfr in esophageal cancer in vivo and in vitro[J].J Cell Biochem,2017,118(9):2625-2634.

张莹,徐兴森,马兴杰.MiR-21对食管癌细胞增殖、凋亡及PI3K/Akt信号通路的影响[J].河北医药,2019,41(7):976-980.

张小三,张一鸣,杨树军,等.微小RNA-150对食管癌细胞增殖、凋亡和PI3K/Akt通路的影响[J].临床肿瘤学杂志,2018,23(11):967-972.

ZENG W,ZHU J F,LIU J Y,et al.miR-133b inhibits cell proliferation,migration and invasion of esophageal squamous cell carcinoma by targeting EGFR[J].Biomed Pharmacother,2019,111:476-484.

GUANEN Q,JUNJIE S,BAOLIN W,et al.MiR-214 promotes cell meastasis and inhibites apoptosis of esophageal squamous cell carcinoma via PI3K/AKT/mTOR signaling pathway[J].Biomed Pharmacother,2018,105:350-361.

司富春,岳静宇.食管鳞癌的中医证候聚类分析[J].中医杂志,2012,53(22):1944-1947.

司富春,刘紫阳.食管癌中医证型和用药规律分析[J].中医学报,2012,27(6):655-657.

贾永森,林清,张艳丽,等.噎膈血瘀证患者血清对食管癌EC9706细胞增殖及PI3K/Akt信号通路蛋白表达的影响[J].现代预防医学,2015,42(22):4143-4146.

田同德,储真真,陈信义.恶性肿瘤高凝状态与血瘀证相关性及中医防治对策研究[J].北京中医药,2009.28(6):425-427.

WU N,DU Z,ZHU Y,et al.The expression and prognostic impact of the PI3K/AKT/mTOR signaling pathway in advanced esophageal squamous cell carcinoma[J].Technol Cancer Res Treat,2018,doi:10.1177/1533033818758772http://dx.doi.org/10.1177/1533033818758772.

AMARAVADI R K.Transcriptional regulation of autophagy in RAS-driven cancers[J].J Clin Invest,2015.125(4):1393-1395.

KONG L,WU Z,ZHAO Y,et al.Qigesan reduces the motility of esophageal cancer cells via inhibiting Gas6/Axl and NF-kappaB expression[J].Biosci Rep,2019,doi:10.1042/BSR20190850http://dx.doi.org/10.1042/BSR20190850.

吴耀松,任闪闪,陈玉龙,等.启膈散对食管癌EC9706细胞株抑制树突状细胞成熟的影响[J].时珍国医国药,2017,28(4):769-772.

吕翠田,董志斌,陈玉龙.启膈散对食管癌小鼠生存质量及免疫调节的影响[J].时珍国医国药,2016,27(8):1806-1809.

崔姗姗,尹素改,吴耀松,等.食管癌EC9706细胞启膈散与六君子汤条件培养基对脐静脉内皮细胞的影响[J].中华中医药杂志,2016,31(4):1230-1233.

司富春.启膈散及其拆方对人食管癌Eca109细胞裸鼠移植瘤血管生成的抑制作用[J].世界华人消化杂志,2008,16(28):3139-3145.

李建省,靳锋,王宝蕊,等.管通方及拆方对人食管癌EC9706细胞增殖和PI3K/AKT信号通路的影响[J].甘肃科技,2017,33(9):94-96.

李建省,靳锋,王宝蕊,等.管通方醇提物对人食管癌EC9706细胞抑制作用的研究[J].西部中医药,2016,29(10):8-10.

吕翠田,司富春,陈玉龙.启膈散、沙参麦冬汤和通幽汤对人食管癌EC9706细胞Caspase-3介导的细胞凋亡信号转导的影响[J].辽宁中医杂志,2016,43(7):1455-1458,1.

吕翠田,陈玉龙,司富春.启膈散、沙参麦冬汤、通幽汤和补气运脾汤对人食管癌EC9706细胞增殖及凋亡的影响[J].中国中医药现代远程教育,2014,12(15):150-153.

司富春.启膈散、沙参麦冬汤、通幽汤和补气运脾汤对hEGF刺激的人食管癌EC9706细胞生长信号转导的调节[J].世界华人消化杂志,2010,18(28):2956-2965.

魏世民.启膈散联合TP化疗方案治疗食管鳞癌临床观察[J].光明中医,2019,34(18):2751-2754.

张玉双,高静,史会娟,等.加味启膈散对食管癌根治术后患者复发转移及生存质量的影响[J].中国全科医学,2018,21(10):1239-1243.

王同甫,张振,姚传山,等.沙参麦冬汤联合化疗对于食管癌患者预后的分析[J].中国中西医结合消化杂志,2019,27(2):119-121,127.

张辉,付吕平.参芪通幽汤合PPF化疗方案治疗中晚期食管癌近远期疗效观察[J].现代中西医结合杂志,2018,27(21):2369-2372.

于耀洋,赵佳,李向楠.南蛇藤提取物联合miR-302通过PI3K/Akt信号通路调控食管癌细胞增殖、侵袭和迁移的研究[J].中草药,2019,50(10):2371-2376.

陈瑞.祛风化痰解毒方及其拆方调节食管癌EC9706细胞PLC-γ1-PI3K信号转导的研究[D].郑州:河南中医学院,2014.

MENG X,DONG X,WANG W,et al.Natural borneol enhances paclitaxel-induced apoptosis of ESCC cells by inactivation of the PI3K/AKT[J].J Food Sci,2018,83(5):1436-1443.

ZHOU J,HAN N,LV G,et al.Two new beta-dihydroagarofuran sesquiterpenes from celastrus orbiculatus thunb and their anti-proliferative activity[J].Molecules,2017,22(6):135-142.

GU Z F,ZHANG Z T,WANG J Y,et al.Icariin exerts inhibitory effects on the growth and metastasis of KYSE70 human esophageal carcinoma cells via PI3K/AKT and STAT3 pathways[J].Environ Toxicol Pharmacol,2017,54:7-13.

LI S,SHEN X Y,OUYANG T,et al.Synergistic anticancer effect of combined crocetin and cisplatin on KYSE-150 cells via p53/p21 pathway[J].Cancer Cell Int,2017,17:98.

涂启敏,黄宏灵,PI3K/AKT/mTOR在姜黄素抑制食管癌细胞增殖中的作用[J].解剖学研究,2018,40(3):174-177.

李秀娟,李玉珍,金春亭,等.姜黄素作用PTEN/PI3K/AKT通路诱导食管癌EC109细胞凋亡[J].中国应用生理学杂志,2015,31(2):174-177.

李秀娟,罗强,孙黎,等.姜黄素对食管癌Ec109细胞增殖和PTEN/PI3K/Akt信号通路的影响[J].中国应用生理学杂志,2015,31(5):465-468.

ZHAO S,JIANG Y,ZHAO J,et al.Quercetin-3-methyl ether inhibits esophageal carcinogenesis by targeting the Akt/mTOR/p70S6K and MAPK pathways[J].Mol Carcinog,2018,57(11):1540-1552.

JIN Z,YAN W,JIN H,et al.Psoralidin inhibits proliferation and enhances apoptosis of human esophageal carcinoma cells via NF-kappaB and PI3K/Akt signaling pathways[J].Oncol Lett,2016,12(2):971-976.

LIU H,ZHAO J,FU R,et al.The ginsenoside Rk3 exerts anti-esophageal cancer activity in vitro and in vivo by mediating apoptosis and autophagy through regulation of the PI3K/Akt/mTOR pathway[J].PLoS One,2019,14(5):e0216759.

ZHANG D,WANG A,FENG J,et al.Ginsenoside Rg5 induces apoptosis in human esophageal cancer cells through the phosphoinositide3 kinase/protein kinase B signaling pathway[J].Mol Med Rep,2019,19(5):4019-4026.

JIANG J H,PI J,JIN H,et al.Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/Akt/mTOR and Ras/Raf pathways[J].J Cell Biochem,2019,120(3):3736-3746.

盛杰霞,邓旭,包军,等.华蟾酥毒基通过FAK/PI3K/Akt通路抑制食管癌Kyse-520细胞迁移和侵袭[J].中国药理学通报,2019,35(1):139-145.

ZHU X,LI Z,LI T,et al.Osthole inhibits the PI3K/Akt signaling pathway via activation of PTEN and induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma[J].Biomed Pharmacother,2018,102:502-509.

ZHANG H B,LU P,GUO Q Y,et al.Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway[J].Oncol Lett,2013,5(2):722-728.

郭琳,程永现,白明,等.冬凌草现代研究分析[J].中医学报,2015,30(3):412-414.

RAJABI H,TAGDE A,ALAM M,et al.DNA methylation by DNMT1 and DNMT3b methyltransferases is driven by the MUC1-C oncoprotein in human carcinoma cells[J].Oncogene,2016,35(50):6439-6445.

KOH H B,SCRUGGS A M,HUANG S K.Transforming growth factor-beta1 increases DNA methyltransferase 1 and 3a expression through distinct post-transcriptional mechanisms in lung fibroblasts[J].J Biol Chem,2016,291(37):19287-19298.

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