苦参碱抗肿瘤活性研究进展
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摘要
苦参是一味传统的中药,在我国药用历史悠久。苦参碱是苦参中主要有效活性成分之一,对各类肿瘤细胞均有较强的抑制作用,已被作为抗肿瘤药物进行了大量的研究。通过相关文献的筛选和分析发现,苦参碱主要通过抑制肿瘤细胞的迁移和侵袭、增殖、改变肿瘤细胞相关蛋白和癌基因的表达、干扰肿瘤细胞周期和诱导肿瘤细胞自噬、凋亡等作用机制,共同参与发挥对肺癌、乳腺癌、肝癌、胃癌、胰腺癌、前列腺癌、白血病、骨髓瘤等的抗癌活性。本文通过对苦参碱抗癌活性及作用机制的发掘,综述其作为抗癌剂的研究进展,为肿瘤的新药研发与临床应用提供有益启示。
Sophora flavescens Ait.is a traditional Chinese medicine with a long history of medicinal use in China. Matrine is one of the main effective active ingredients in Sophora flavescens. It has strong inhibitory effects on various tumor cells and has been extensively studied as an antitumor drug. Through screening and analysis of related literatures, it is found that matrine mainly inhibits tumor cell migration and invasion, proliferation, changes of tumor cell-associated protein and oncogene expression, interferes with tumor cell cycle and induces autophagy and apoptosis of tumor cells. Mechanism, participate in the anti-cancer activity of lung cancer, breast cancer, liver cancer, stomach cancer, pancreatic cancer, prostate cancer, leukemia, myeloma, etc. In this paper, through the exploration of the anti-cancer activity and mechanism of matrine, the research progress of its anticancer agent is reviewed, which provides useful enlightenment for the development and clinical application of new drugs.
Sophora flavescens Ait.is a traditional Chinese medicine with a long history of medicinal use in China. Matrine is one of the main effective active ingredients in Sophora flavescens. It has strong inhibitory effects on various tumor cells and has been extensively studied as an antitumor drug. Through screening and analysis of related literatures, it is found that matrine mainly inhibits tumor cell migration and invasion, proliferation, changes of tumor cell-associated protein and oncogene expression, interferes with tumor cell cycle and induces autophagy and apoptosis of tumor cells. Mechanism, participate in the anti-cancer activity of lung cancer, breast cancer, liver cancer, stomach cancer, pancreatic cancer, prostate cancer, leukemia, myeloma, etc. In this paper, through the exploration of the anti-cancer activity and mechanism of matrine, the research progress of its anticancer agent is reviewed, which provides useful enlightenment for the development and clinical application of new drugs.
引文
[1]Rashid Haroon Ur,Xu Yiming,Muhammad Yaseen,et al.Research advances on anticancer activities of matrine and its derivatives:An updated overview[J].European journal of medicinal chemistry,2018,161:205-238.
[2]He.XR,Fang.JC,Huang.et al.Sophora flavescens Ait.:Traditional usage,phytochemistry and pharmacology of an important traditional Chinese medicine[J].Journal of ethnopharmacology,2015,172:10-29.
[3]刘晶晶,牟艳玲.苦参碱抗肿瘤作用机制的研究进展[J].中国药房,2017,28(19):2707-2711.
[4]李媛秋,刘剑君,么鸿雁.肺癌发病和死亡流行情况与人类发展指数的关系分析[J/OL].中国肿瘤,2019,1:1-5.
[5]J.Yang,Y.P.Du He,H.Zhong,et al.Matrine suppresses the migration and invasion of nsclc cells by inhibiting PaX2-induced epithelial-mesenchymal transition[J].Onco Targets Ther,2017,10:5209-5217.
[6]方彪彪,张淑君,刘佳,等.苦参碱可能通过自噬抑制肺癌A549细胞的增殖[J].现代肿瘤医学,2018,26(12):1811-1815.
[7]吴幸谕,李劲,黄光位,等.复方苦参碱联合甘露聚糖肽胸腔灌注治疗肺癌伴恶性胸腔积液的疗效观察[J].慢性病学杂志,2018,19(04):423-424.
[8]D.C.E.,M.Jiemin,G.S.Ann,et al.Breast cancer statistics,2017,racial disparity in mortality by state[J].Cancer J.Clin,2017,67:439-448.
[9]H.Li,X.Li,M.Bai,et al.Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2[J].International journal of experimental pathology,2015,8:14793-14799.
[10]肖旭,敖曼,石文达,等.苦参碱对乳腺癌Bcap-37细胞增殖和凋亡的影响[J].中成药,2018,12:2750-2754.
[11]张瑞奎,汪超.苦参碱对大鼠乳腺癌细胞荷瘤生长及其炎性因子与免疫功能的影响[J].中国应用生理学杂志,2018,34(04):375-378.
[12]N.Zhou,J.Li,T.Li,et al.Matrine induced apoptosis in Hep3B cells-via the inhibition of MDM2[J].Molecular Medicine Reports,2017,15(1):442-450.
[13]W.Zhou,X.Xu,J.Gao,et al.TCM matrine induces cell arrest and apoptosis with recovery expression of the hepato-specific miR122a in human hepatocellular carcinoma Hep G2cell line[J].Int J Clin Exp Pathol,2015,8:9004-9012.
[14]X.Zhang,H.Yu.Matrine inhibits diethylnitrosamine-induced HCCproliferation in rats through inducing apoptosis via p53,Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression[J].Iranian journal of pharmaceutical research,2016,15:491-499.
[15]Wang.Y,Liu.YH,Jiang.JS,et al.Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC-7721 cell line[J].Oncology Letters,2018,15(2):1777-1782.
[16]鄂颖,尚德高,尤胜.苦参碱联合顺铂对人肝癌细胞株HepG2裸鼠移植瘤模型瘤体生长及caspase-3和Survivin表达的影响[J].临床和实验医学杂志,2019,18(05):457-460.
[17]杨静波,李宏杰.苦参碱和氧化苦参碱对肝癌细胞增殖和凋亡的影响[J].中国临床药理学杂志,2018,34(09):1067-1069.
[18]曹建,魏润杰,邓茹芸,等.苦参碱及氧化苦参碱抑制肿瘤作用机制研究进展及展望[J].中草药,2019,50(03):753-760.
[19]黄谋珍,刘涛,白俊,等.探究PHA-L共诱导的CIK细胞的生物学特性及其联合苦参碱体外抗胃癌效应[J].免疫学杂志,2017,33(06):488-491+518.
[20]梁辰,戴静,周福祥,等.苦参碱促进胃癌细胞凋亡及对STAT3、Cleaved-caspase3、MMP-2蛋白表达的影响[J].肿瘤药学,2017,7(01):28-32.
[21]何春游,张法灿,郭先文,等.苦参碱对胰腺癌CFPAC-1细胞增殖、凋亡及Hedgehog信号通路的影响[J].世界华人消化杂志,2016,24(03):338-346.
[22]Y.Ma,F.Zou,J.Xiong,et al.Effectof Matrine on HPAC cell migration by down-regulating the expression of MT1-MMP via Wnt signaling[J].Cancer Cell International,2015,15:2-7.
[23]H.Huang,Q.Wang,T.Du,et al.Matrine inhibits the progression of prostate cancer by promoting expression of GADD45B[J].Prostate,2018,78(5):327-335.
[24]J.Chang,S.Hu,W.Wang,et al.Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition[J].Molecular Medicine Report,2018,18(1):945-957.
[25]胡美薇,傅丽娟,范翠华,等.苦参碱诱导人白血病耐药细胞K562/IM自噬和凋亡的研究[J].中国中西医结合杂志,2018,38(02):213-218.
[26]A.T.Vardarli,Z.Düzgün,C.Erdem,et al.Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia(T-ALL)cells[J].Bosnian Journal Of Basic Medical Sciences,2018,18(2):141-149.
[27]M.Aghvami,F.Ebrahimi,M.H.Zarei,et al.Matrine Induction of ROS Mediated Apoptosis in Human ALL B-lymphocytes Via Mitochondrial Targeting[J].Asian Pac J Cancer Prev,2018,19:555-560.
[28]J.Lv,L.Xu,Z.Wang,R.Ma,Q.Li,M.Zheng,M.Li,H.Chen,H.Yu,J.Liu.Effects of matrine on the proliferation and apoptosis of myeloma RPMI8226 cells[J].Int.J.Clin.Exp.Pathol,2016,9:6501-6505.
[29]杨春秀,陈建斌.苦参碱抑制RPMI8226细胞增殖及对Notch通路的影响[J].中成药,2017,39(10):2167-2170.
[30]Y.Yang,J.Guo,Z.Shao,J.Gao.Matrine inhibits bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway:An experimental study[J].Asian Pacific journal of cancer prevention,2017,10(5):515-519.
[31]X.Wu,J.Zhou,D.Cai,et al.Matrine inhibits the metastatic properties of human cervical cancer cells via downregulating the p38 signaling pathway[J].Oncology Reports,2017,38(2):1312-1320.
[32]J-H.Jiang,J.Pi,H.Jin,et al.Chinese herb medicine matrine induce apoptosis in human esophageal squamous cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting mitochondrial function[J].Pathology,Research And Practice,2018,214(5):691-699.
[2]He.XR,Fang.JC,Huang.et al.Sophora flavescens Ait.:Traditional usage,phytochemistry and pharmacology of an important traditional Chinese medicine[J].Journal of ethnopharmacology,2015,172:10-29.
[3]刘晶晶,牟艳玲.苦参碱抗肿瘤作用机制的研究进展[J].中国药房,2017,28(19):2707-2711.
[4]李媛秋,刘剑君,么鸿雁.肺癌发病和死亡流行情况与人类发展指数的关系分析[J/OL].中国肿瘤,2019,1:1-5.
[5]J.Yang,Y.P.Du He,H.Zhong,et al.Matrine suppresses the migration and invasion of nsclc cells by inhibiting PaX2-induced epithelial-mesenchymal transition[J].Onco Targets Ther,2017,10:5209-5217.
[6]方彪彪,张淑君,刘佳,等.苦参碱可能通过自噬抑制肺癌A549细胞的增殖[J].现代肿瘤医学,2018,26(12):1811-1815.
[7]吴幸谕,李劲,黄光位,等.复方苦参碱联合甘露聚糖肽胸腔灌注治疗肺癌伴恶性胸腔积液的疗效观察[J].慢性病学杂志,2018,19(04):423-424.
[8]D.C.E.,M.Jiemin,G.S.Ann,et al.Breast cancer statistics,2017,racial disparity in mortality by state[J].Cancer J.Clin,2017,67:439-448.
[9]H.Li,X.Li,M.Bai,et al.Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2[J].International journal of experimental pathology,2015,8:14793-14799.
[10]肖旭,敖曼,石文达,等.苦参碱对乳腺癌Bcap-37细胞增殖和凋亡的影响[J].中成药,2018,12:2750-2754.
[11]张瑞奎,汪超.苦参碱对大鼠乳腺癌细胞荷瘤生长及其炎性因子与免疫功能的影响[J].中国应用生理学杂志,2018,34(04):375-378.
[12]N.Zhou,J.Li,T.Li,et al.Matrine induced apoptosis in Hep3B cells-via the inhibition of MDM2[J].Molecular Medicine Reports,2017,15(1):442-450.
[13]W.Zhou,X.Xu,J.Gao,et al.TCM matrine induces cell arrest and apoptosis with recovery expression of the hepato-specific miR122a in human hepatocellular carcinoma Hep G2cell line[J].Int J Clin Exp Pathol,2015,8:9004-9012.
[14]X.Zhang,H.Yu.Matrine inhibits diethylnitrosamine-induced HCCproliferation in rats through inducing apoptosis via p53,Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression[J].Iranian journal of pharmaceutical research,2016,15:491-499.
[15]Wang.Y,Liu.YH,Jiang.JS,et al.Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC-7721 cell line[J].Oncology Letters,2018,15(2):1777-1782.
[16]鄂颖,尚德高,尤胜.苦参碱联合顺铂对人肝癌细胞株HepG2裸鼠移植瘤模型瘤体生长及caspase-3和Survivin表达的影响[J].临床和实验医学杂志,2019,18(05):457-460.
[17]杨静波,李宏杰.苦参碱和氧化苦参碱对肝癌细胞增殖和凋亡的影响[J].中国临床药理学杂志,2018,34(09):1067-1069.
[18]曹建,魏润杰,邓茹芸,等.苦参碱及氧化苦参碱抑制肿瘤作用机制研究进展及展望[J].中草药,2019,50(03):753-760.
[19]黄谋珍,刘涛,白俊,等.探究PHA-L共诱导的CIK细胞的生物学特性及其联合苦参碱体外抗胃癌效应[J].免疫学杂志,2017,33(06):488-491+518.
[20]梁辰,戴静,周福祥,等.苦参碱促进胃癌细胞凋亡及对STAT3、Cleaved-caspase3、MMP-2蛋白表达的影响[J].肿瘤药学,2017,7(01):28-32.
[21]何春游,张法灿,郭先文,等.苦参碱对胰腺癌CFPAC-1细胞增殖、凋亡及Hedgehog信号通路的影响[J].世界华人消化杂志,2016,24(03):338-346.
[22]Y.Ma,F.Zou,J.Xiong,et al.Effectof Matrine on HPAC cell migration by down-regulating the expression of MT1-MMP via Wnt signaling[J].Cancer Cell International,2015,15:2-7.
[23]H.Huang,Q.Wang,T.Du,et al.Matrine inhibits the progression of prostate cancer by promoting expression of GADD45B[J].Prostate,2018,78(5):327-335.
[24]J.Chang,S.Hu,W.Wang,et al.Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition[J].Molecular Medicine Report,2018,18(1):945-957.
[25]胡美薇,傅丽娟,范翠华,等.苦参碱诱导人白血病耐药细胞K562/IM自噬和凋亡的研究[J].中国中西医结合杂志,2018,38(02):213-218.
[26]A.T.Vardarli,Z.Düzgün,C.Erdem,et al.Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia(T-ALL)cells[J].Bosnian Journal Of Basic Medical Sciences,2018,18(2):141-149.
[27]M.Aghvami,F.Ebrahimi,M.H.Zarei,et al.Matrine Induction of ROS Mediated Apoptosis in Human ALL B-lymphocytes Via Mitochondrial Targeting[J].Asian Pac J Cancer Prev,2018,19:555-560.
[28]J.Lv,L.Xu,Z.Wang,R.Ma,Q.Li,M.Zheng,M.Li,H.Chen,H.Yu,J.Liu.Effects of matrine on the proliferation and apoptosis of myeloma RPMI8226 cells[J].Int.J.Clin.Exp.Pathol,2016,9:6501-6505.
[29]杨春秀,陈建斌.苦参碱抑制RPMI8226细胞增殖及对Notch通路的影响[J].中成药,2017,39(10):2167-2170.
[30]Y.Yang,J.Guo,Z.Shao,J.Gao.Matrine inhibits bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway:An experimental study[J].Asian Pacific journal of cancer prevention,2017,10(5):515-519.
[31]X.Wu,J.Zhou,D.Cai,et al.Matrine inhibits the metastatic properties of human cervical cancer cells via downregulating the p38 signaling pathway[J].Oncology Reports,2017,38(2):1312-1320.
[32]J-H.Jiang,J.Pi,H.Jin,et al.Chinese herb medicine matrine induce apoptosis in human esophageal squamous cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting mitochondrial function[J].Pathology,Research And Practice,2018,214(5):691-699.