中药调节信号转导通路诱导肿瘤细胞自噬的实验研究进展
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摘要
自噬是以细胞质内出现自噬小体为特征的细胞自我消化和吸收的过程,是影响肿瘤发生发展过程的关键因素,具有抑癌和促癌的双重调节作用,且多条信号转导通路参与调控肿瘤细胞自噬。已证实多种中药及其活性成分、中药复方具有显著的抗肿瘤作用,其机制可能与诱导肿瘤细胞自噬有关。对肿瘤细胞自噬相关的信号转导通路进行分析和总结,并从PI3K/AKT-mTOR、AMPK、MAPK、Beclin-l、Wnt/β-catenin等通路综述中药诱导自噬、抗肿瘤的分子机制。
Autophagy is a process of self-digestion and absorption of cells,which characterized by autophagosomes in the cytoplasm. It is a key factor affecting the process of tumorigenesis and development. It shows the dual regulatory roles of anti-cancer and promoting cancer. Multiple signal transduction pathways involve in and regulate the autophagy of tumor cells. Various Chinese medicine and their active ingredients,as well as compound recipes,have been confirmed to have obvious anti-tumor effects,and their mechanisms may be related to inducing tumor cell autophagy. In this paper,the signal transduction pathways related to autophagy of tumor cells are analyzed and summarized,and the molecular mechanisms of Chinese medicine on inducing autophagy and anti-tumor are reviewed from PI3 K/AKT-mTOR,AMPK,MAPK,Beclin-l,Wnt/β-catenin signaling pathways.
Autophagy is a process of self-digestion and absorption of cells,which characterized by autophagosomes in the cytoplasm. It is a key factor affecting the process of tumorigenesis and development. It shows the dual regulatory roles of anti-cancer and promoting cancer. Multiple signal transduction pathways involve in and regulate the autophagy of tumor cells. Various Chinese medicine and their active ingredients,as well as compound recipes,have been confirmed to have obvious anti-tumor effects,and their mechanisms may be related to inducing tumor cell autophagy. In this paper,the signal transduction pathways related to autophagy of tumor cells are analyzed and summarized,and the molecular mechanisms of Chinese medicine on inducing autophagy and anti-tumor are reviewed from PI3 K/AKT-mTOR,AMPK,MAPK,Beclin-l,Wnt/β-catenin signaling pathways.
引文
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[26] ZHANG L D,LIU Z,LIU H,et al. Oridonin enhances the anticancer activity of NVP- BEZ235 against neuroblastoma cells in vitro and in vivo through autophagy[J].Int J Oncol,2016,49(2):657- 665.
[27] PAGAKI E,PATSOURIS E,GONIDI M,et al. The value of E- cadherin/β- catenin expression in imprints of NSCLC:relationship with clinicopathological factors[J].Diagn Cytopathol,2010,38(6):419- 424.
[28] FU Y,CHANG H,PENG X,et al. Resveratrol inhibits breast cancer stem- like cells and induces autophagy via suppressing Wnt/β- catenin signaling pathway[J].PLoS One,2014,9(7):e102535.
[29] ZHANG Z,LIU T,YU M,et al. The plant alkaloid tetrandrine inhibits metastasis via autophagy- dependent Wnt/β- catenin and metastatic tumor antigen 1 signaling in human liver cancer cells[J].J Exp Clin Cancer Res,2018,37(1):7.
[30] 付婉,董笛,赵颖.自噬的相关分子机制[J].中国生物化学与分子生物学报,2017,33(5):448- 455.
[31] 孙雅婧,郭青龙.细胞自噬的研究进展[J].药学与临床研究,2012,20(3):236- 239.
[32] 高雅,邢皓,于爱鸣.自噬与肿瘤[J].中国科技信息,2012(14):115.
[33] 刘杰民,纪云西,蒋历,等.细胞自噬是探索中医药微观机制的新思路[J].时珍国医国药,2013,24(2):425- 426.
[2] 张甘霖,杨国旺,于明薇,等.自噬——中医药抗肿瘤研究的新方向[J].中华中医药杂志,2014,29(2):507- 510.
[3] ZHANG H,LEI Y,YUAN P,et al. ROS- mediated autophagy induced by dysregulation of lipid metabolism plays a protective role in colorectal cancer cells treated with gambogic acid [J].PLoS One,2014,9(5):e96418.
[4] LU J,SUN D,GAO S,et al. Cyclovirobuxine D induces autophagy- associated cell death via the Akt/mTOR pathway in MCF- 7 human breast cancer cells[J].J Pharmacol Sci,2014,125(1):74- 82.
[5] LI Y R,LI S,HO CT,et al. Tangeretin derivative,5- acetyloxy- 6,7,8,4’- tetramethoxyflavone induces G2/M arrest,apoptosis and autophagy in human non- small cell lung cancer cells in vitro and in vivo[J].Cancer Biol Ther,2016,17(1):48- 64.
[6] LI C,CHEN J,LU B,et al. Molecular switch role of Akt in Polygonatum odoratum lectin- induced apoptosis and autophagy in human non- small cell lung cancer A549 cells [J].PLoS One,2014,9(7):e101526.
[7] CAI Y,XU P,YANG L,et al. HMGB1- mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells[J].Sci Rep,2016,6:37845.
[8] ZOU N,WEI Y,LI F,et al. The inhibitory effects of compound Muniziqi granule against B16 cells and harmine induced autophagy and apoptosis by inhibiting Akt/mTOR pathway[J].BMC Complement Altern Med,2017,17(1):517.
[9] WANG Y F,LI T,TANG Z H,et al. Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells[J].Phytother Res,2015,29(5):674- 679.
[10] 梁君伟,方志华,李青山.二甲双胍联合紫杉醇对人乳腺癌细胞凋亡及AMPK信号通路的影响[J].中国病理生理杂志,2018,34(12):2186- 2192.
[11] SHEN S,ZHANG Y,WANG Z,et al. Bufalin induces the interplay between apoptosis and autophagy in glioma cells through endoplasmic reticulum stress[J].Int J Biol Sci,2014,10(2):212- 224.
[12] 陆明.牛蒡子苷元对结肠癌细胞及小鼠脾细胞的作用和机制[D].合肥:安徽医科大学,2014.
[13] WANG H,WANG F,WU S,et al. Traditional herbal medicine- derived sulforaphene promotes mitophagic cell death in lymphoma cells through CRM1- mediated p62/SQSTM1 accumulation and AMPK activation[J].Chem Biol Interact,2018,281:11- 23.
[14] LAM W,JIANG Z,GUAN F,et al. PHY906 (KD018),an adjuvant based on a 1800- year- old Chinese medicine,enhanced the anti- tumor activity of Sorafenib by changing the tumor microenvironment[J].Sci Rep,2015,5:9384.
[15] SHEN S,ZHANG Y,ZHANG R,et al. Ursolic acid induces autophagy in U87MG cells via ROS- dependent endoplasmic reticulum stress[J].Chem Biol Interact,2014,218(2):28- 41.
[16] WEN J H. Ursolic acid:Pharmacokinetics process in vitro and in vivo,a mini review [J].Arch Pharm (Weinheim),2019.doi:10.1002/ardp.201800222.
[17] XAVIER C P,LIMA C F,PEDRO D F,et al. Ursolic acid induces cell death and modulates autophagy through JNK pathway in apoptosis- resistant colorectal cancer cells[J].J Nutr Biochem,2013,24(4):706- 712.
[18] LI T,XU X H,TANG Z H,et al. Platycodin D induces apoptosis and triggers ERK- and JNK- mediated autophagy in human hepatocellular carcinoma BEL- 7402 cells[J].Acta Pharmacol Sin,2015,36(12):1503- 1513.
[19] CHEN J L,CHANG C J,WANG J Y,et al. In Vitro and In Vivo Effects of Jia- Wei- Xiao- Yao- San in Human Breast Cancer MCF- 7 Cells Treated With Tamoxifen[J].Integr Cancer Ther,2014,13(3):226- 239.
[20] SUN Y,ZOU M,HU C,et al. Wogonoside induces autophagy in MDA- MB- 231 cells by regulating MAPK mTOR pathway[J].Food Chem Toxicol,2013,51(1):53- 60.
[21] TANG Z H,LI T,CHANG L L,et al. Glycyrrhetinic Acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells[J].J Agric Food Chem,2014,62(49):11910- 11916.
[22] YUE Z,JIN S,YANG C,et al. Beclin 1,an autophagy gene essential for early embryonic development,is a haplonisufficient tumor suppressor[J].Proc Natl Acad Sci USA,2003,100(25):15077- 15082.
[23] LIEN J C,LIN M W,CHANG S J,et al. Tetrandrine induces programmed cell death in human oral cancer CAL 27 cells through the reactive oxygen species production and caspase- dependent pathways and associated with beclin- 1- induced cell autophagy[J].Environ Toxicol,2016,32(1):329- 343.
[24] 汪伦记,许美秋,纠敏,等.冬凌草提取物对金黄色葡萄球菌生物膜形成的抑制作用[J].天然产物研究与开发,2017,29(6):104- 109.
[25] 陈婉琪,张鸿,王进峰,等.冬凌草毛状根的优化培养及其提取物的肿瘤细胞增殖抑制活性检测[J].生物技术通报,2018,34(10):122- 128.
[26] ZHANG L D,LIU Z,LIU H,et al. Oridonin enhances the anticancer activity of NVP- BEZ235 against neuroblastoma cells in vitro and in vivo through autophagy[J].Int J Oncol,2016,49(2):657- 665.
[27] PAGAKI E,PATSOURIS E,GONIDI M,et al. The value of E- cadherin/β- catenin expression in imprints of NSCLC:relationship with clinicopathological factors[J].Diagn Cytopathol,2010,38(6):419- 424.
[28] FU Y,CHANG H,PENG X,et al. Resveratrol inhibits breast cancer stem- like cells and induces autophagy via suppressing Wnt/β- catenin signaling pathway[J].PLoS One,2014,9(7):e102535.
[29] ZHANG Z,LIU T,YU M,et al. The plant alkaloid tetrandrine inhibits metastasis via autophagy- dependent Wnt/β- catenin and metastatic tumor antigen 1 signaling in human liver cancer cells[J].J Exp Clin Cancer Res,2018,37(1):7.
[30] 付婉,董笛,赵颖.自噬的相关分子机制[J].中国生物化学与分子生物学报,2017,33(5):448- 455.
[31] 孙雅婧,郭青龙.细胞自噬的研究进展[J].药学与临床研究,2012,20(3):236- 239.
[32] 高雅,邢皓,于爱鸣.自噬与肿瘤[J].中国科技信息,2012(14):115.
[33] 刘杰民,纪云西,蒋历,等.细胞自噬是探索中医药微观机制的新思路[J].时珍国医国药,2013,24(2):425- 426.