基于TCMSP抗肿瘤中药小分子EGFR-TKI的研究
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摘要
目的研究分析中药小分子表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)的抗肿瘤情况。方法挖掘中药系统药理学数据库与分析平台(TCMSP)中药小分子表皮生长因子受体抑制剂,利用反向分子对接服务器(DRAR-CPI)进行靶点验证。结果木犀草素、槲皮素、金雀异黄酮、表没食子儿茶素没食子酸酯、漆黄素5种中药小分子与表皮生长因子受体(EGFR)结合良好。结论中药小分子EGFR-TKI能从多个靶点、多种途径抑制肿瘤细胞的生长和扩散,利用中药小分子开发新一代多靶点EGFR-TKI具有广阔的前景。
Objective: To study the status of the anti-tumor small molecule epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) from Chinese medicine. Methods: We collected the Chinese medicine small molecule EGFR-TKI based on traditional Chinese medicine pharmacology system technology platform(TCMSP), and predicted their targets using reverse molecular docking server(DRAR-CPI). Results: Luteolin, quercetin, genistein, epigallocatechin-3-gallate, fisetin could interact with the EGFR well. Conclusion: Chinese medicine small molecule EGFR-TKI could inhibit the growth and proliferation of tumor cell by multiple targets and approaches. It has a broad prospect using traditional Chinese medicine small molecules to develop a new generation of multiple targets EGFR-TKI.
Objective: To study the status of the anti-tumor small molecule epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) from Chinese medicine. Methods: We collected the Chinese medicine small molecule EGFR-TKI based on traditional Chinese medicine pharmacology system technology platform(TCMSP), and predicted their targets using reverse molecular docking server(DRAR-CPI). Results: Luteolin, quercetin, genistein, epigallocatechin-3-gallate, fisetin could interact with the EGFR well. Conclusion: Chinese medicine small molecule EGFR-TKI could inhibit the growth and proliferation of tumor cell by multiple targets and approaches. It has a broad prospect using traditional Chinese medicine small molecules to develop a new generation of multiple targets EGFR-TKI.
引文
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[14]李正红,梁生林,钟兴华.葎草提取物胃肠促动作用的实验研究[J].井冈山大学学报:自然科学版,2016,37(6):83-88.
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[17]洪专.木犀草素治疗EGFR受体继发性突变的非小细胞肺癌的实验研究[D].南京:南京大学,2014.
[18]蒋建宏,周菊峰,胡钞粟,等.槲皮素镧配合物对S.Pombe细胞生长代谢热动力学的影响[J].井冈山大学学报:自然科学版,2015,36(2):20-24.
[19]王建全,张亚娜,林敏.乙醇/硫酸铵双水相体系分离纯化款冬花总黄酮[J].井冈山大学学报:自然科学版,2016,37(1):40-45.
[20]吴波,易剑峰,陈婷.中药对类风湿性关节炎信号传导通路的调节概况[J].宜春学院学报,2013,35(6):5-9.
[21]向廷秀,陶小红,姜政,等.槲皮素对SGC-7901胃癌细胞生长及HSP70和EGFR表达的影响[J].西安交通大学学报:医学版,2007,28(7):411-414.
[22]李士坤,陈克河,任庆梅.槲皮素对人食管癌Eca-109细胞的分化诱导作用[J].中国实用医药,2007,2(36):14-15.
[23]袁江兰,刘晖,康旭,等.表皮生长因子受体酪氨酸激酶结构域与其抑制剂染料木素的模拟对接[J].生物工程学报,2008,24(10):1813-1817.
[24]Wu B W,Wu Y,Wang J L,et al.Study on the mechanism of epidermal growth factor-induced proliferation of hepatoma cells[J].World J Gastroenterol,2003,9(2):271-275.
[25]陈丽莉,苏俭生.EGCG抗癌靶点中酪氨酸激酶受体RTKs的研究进展[J].同济大学学报:医学版,2011,32(3):116-119.
[26]陈丽莉,苏俭生.EGCG对舌鳞癌细胞CAL-27的EGFR、67LR及VEGF表达的影响[J].口腔颌面外科杂志,2012,22(4):238-241.
[27]Suh Y,Afaq F,Johnson J J,et al.A plant flavonoid fisetin induces apop-tosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappa B-signaling pathways[J].Carcinogenesis,2009,30(2):300.
[2]Naik D S,Sharma S,Ray A,et al.Epidermal growthfactor receptor expression in urinary bladder cancer[J].Ind J Urol,2011,27(2):208-214.
[3]Hwangbo W,Lee J H,Ahn S,et al.EGFR gene amplification and protein expression in invasive ductal carcinoma of the breast[J].Korean J Pathol,2013,47(2):107-115.
[4]孙栋勋,蔡志毅.EGFR/PI3K/Akt细胞信号传导通路与肿瘤[J].检验医学,2014,29(7):768-773.
[5]姚玉霜,张婷婷,戚玉言,等.卵巢癌组织EGFR及下游信号分子的表达及其临床意义[J].中华肿瘤防治杂志,2011,18(3):212-215.
[6]孔维佳,蒋建东.以EGFR家族受体酪氨酸激酶为靶点的抗肿瘤治疗研究进展[J].中国药理学通报,2003,19(8):847-851.
[7]Zhou C,Wu Y L,Chen G,et al.Final overall survival results from a randomised,phaseⅢstudy of erlotinib versus chemotherapy as first-linetreatment of EGFR mutation-positive advanced non-small cell lung cancer(OPTIMAL,CTONE-0802)[J].Ann Oncol,2015,26(9):1877-1883.
[8]Yang H,Wang L,Zhao J,et al.TGF-βactivated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer[J].Lung cancer,2015,87(3):249-257.
[9]杨雅琼,李宗海.以EGFR为靶点的肿瘤分子靶向药物研究进展[J].中国生物工程杂志,2012,32(5):91-96.
[10]屈睿.多靶点抗肿瘤天然活性成分筛选及其抑瘤活性研究[D].镇江:江苏大学,2014.
[11]项杰.EGFR酪氨酸激酶抑制剂的设计、合成及生物活性研究[D].上海:华东理工大学,2012.
[12]任伟光,林森森,李文涛,等.UPLCQ-TOF/MS法研究艾叶抑制EGFR激酶的活性部位[J].华西药学杂志,2013,28(6):604-606.
[13]汝锦龙.中药系统药理学数据库和分析平台的构建和应用[D].杨凌:西北农林科技大学,2015.
[14]李正红,梁生林,钟兴华.葎草提取物胃肠促动作用的实验研究[J].井冈山大学学报:自然科学版,2016,37(6):83-88.
[15]石天松.三种裸花紫珠制剂中木犀草素的测定[J].中成药,2011,33(11):2015-2017.
[16]隋佳琪.木犀草素通过EGFR信号通路发挥抗乳腺癌作用的机制及其与ERα/IGF-1R的关系[D].大连:辽宁师范大学,2016.
[17]洪专.木犀草素治疗EGFR受体继发性突变的非小细胞肺癌的实验研究[D].南京:南京大学,2014.
[18]蒋建宏,周菊峰,胡钞粟,等.槲皮素镧配合物对S.Pombe细胞生长代谢热动力学的影响[J].井冈山大学学报:自然科学版,2015,36(2):20-24.
[19]王建全,张亚娜,林敏.乙醇/硫酸铵双水相体系分离纯化款冬花总黄酮[J].井冈山大学学报:自然科学版,2016,37(1):40-45.
[20]吴波,易剑峰,陈婷.中药对类风湿性关节炎信号传导通路的调节概况[J].宜春学院学报,2013,35(6):5-9.
[21]向廷秀,陶小红,姜政,等.槲皮素对SGC-7901胃癌细胞生长及HSP70和EGFR表达的影响[J].西安交通大学学报:医学版,2007,28(7):411-414.
[22]李士坤,陈克河,任庆梅.槲皮素对人食管癌Eca-109细胞的分化诱导作用[J].中国实用医药,2007,2(36):14-15.
[23]袁江兰,刘晖,康旭,等.表皮生长因子受体酪氨酸激酶结构域与其抑制剂染料木素的模拟对接[J].生物工程学报,2008,24(10):1813-1817.
[24]Wu B W,Wu Y,Wang J L,et al.Study on the mechanism of epidermal growth factor-induced proliferation of hepatoma cells[J].World J Gastroenterol,2003,9(2):271-275.
[25]陈丽莉,苏俭生.EGCG抗癌靶点中酪氨酸激酶受体RTKs的研究进展[J].同济大学学报:医学版,2011,32(3):116-119.
[26]陈丽莉,苏俭生.EGCG对舌鳞癌细胞CAL-27的EGFR、67LR及VEGF表达的影响[J].口腔颌面外科杂志,2012,22(4):238-241.
[27]Suh Y,Afaq F,Johnson J J,et al.A plant flavonoid fisetin induces apop-tosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappa B-signaling pathways[J].Carcinogenesis,2009,30(2):300.