MAPK信号通路影响肿瘤多药耐药的研究进展
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摘要
临床肿瘤治疗中,化疗药物在一定程度上抑制了肿瘤的生长和转移,但随着化疗药物的长期使用,肿瘤细胞会产生多药耐药(multidrug resistance,MDR)现象,导致化疗失败。肿瘤耐药的分子机制很复杂,包括ABC转运蛋白超家族的异常表达、细胞凋亡抑制、信号通路异常活化等。近年来,研究认为丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路可能参与了肿瘤耐药的形成。本文主要对MAPK信号转导通路影响肿瘤多药耐药以及通路抑制剂逆转耐药的研究进展作一综述。
In clinical treatment of tumors,chemotherapeutic drugs inhibit the growth and metastasis of tumors. However,with the long-term use of chemotherpeutic drugs,multidrug resistance (MDR) causes treatment failure. The molecular mechanisms of drug resistance are complex,including abnormal expression of ABC transporter superfamily members,inhibition of apoptosis and abnormal activation of signaling pathways. In recent years,it is suggested that mitogen-activated protein kinases (MAPK) signaling pathway may be involved in drug resistance.This article summarized the research progresses of MAPK signal transduction pathways affecting multidrug resistance and pathway inhibitors reversing drug resistance in tumors.
In clinical treatment of tumors,chemotherapeutic drugs inhibit the growth and metastasis of tumors. However,with the long-term use of chemotherpeutic drugs,multidrug resistance (MDR) causes treatment failure. The molecular mechanisms of drug resistance are complex,including abnormal expression of ABC transporter superfamily members,inhibition of apoptosis and abnormal activation of signaling pathways. In recent years,it is suggested that mitogen-activated protein kinases (MAPK) signaling pathway may be involved in drug resistance.This article summarized the research progresses of MAPK signal transduction pathways affecting multidrug resistance and pathway inhibitors reversing drug resistance in tumors.
引文
[1]WANG B,KRALL EB,AGUIRRE AJ,et al.ATXN1L,CIC,and ETS transcription factors modulate sensitivity to MAPK pathway inhibition[J].Cell Rep,2017,18(6):1543-1557.
[2]SHAO Y,WANG C,HONG Z,et al.Inhibition of p38 mitogenactivated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats[J].J Neurochem,2016,136(5):1096-1105.
[3]刘树人.硫化物应激下单环刺螠MAPK信号通路的功能初探[D].青岛:中国海洋大学,2015.
[4]龚小卫,姜勇.丝裂原活化蛋白激酶(MAPK)生物学功能的结构基础[J].中国生物化学与分子生物学报,2003,19(1):5-11.
[5]WANG Z,HARKINS PC,ULEVITCH RJ,et al.The structure of mitogen-activated protein kinase p38 at 2.1-A resolution[J].Proc Nati Acad Sci USA,1997,94(6):2327-2332.
[6]AKASAKA E,TAKEKOSHI S,HORIKOSHI Y,et al.Protein oxidative damage and heme oxygenase in sunlight-exposed human skin:roles of MAPK responses to oxidative stress[J].Tokai JExp Clin Med,2010,35(4):152-164.
[7]NIX P,HISAMOTO N,MATSUMOTO K,et al.Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways[J].Proc Natl Acad Sci USA,2011,108(26):10738-10743.
[8]JIN W,LU Y,LI Q,et al.Down-regulation of the P-glycoprotein relevant for multidrug resistance by intracellular acidification through the crosstalk of MAPK signaling pathways[J].Int J Biochem Cell Biol,2014,54(8):111-121.
[9]张宗峰,王红丽,时小丁,等.表皮生长因子受体通过MAPK/ERK信号通路调节基质金属蛋白酶1表达的研究[J].国际免疫学杂志,2015,38(6):517-521.
[10]AMANDA T,ZAITUN Z,CAITRN OL,et al.Inhibition of multidrug resistance protein 1(MRP1)improves chemotherapy drug response in primary and recurrent glioblastoma multiforme[J].Front Neurosci,2015,9:218-227.
[11]KATAYAMA K,YOSHIOKA S,TSUKAHARA S,et al.Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein[J].Mol Cancer Ther,2007,6(7):2092-2102.
[12]MENG Q,HE X,XIE G,et al.MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells[J].Oncol Lett,2017,14(3):3089-3095.
[13]MCCUBREY JA,STEELMAN LS,ABRAMS SL,et al.Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance[J].Adv Enzyme Regul,2006,46(1):249-279.
[14]DING S,CHAMBERLAIN M,MCLAREN A,et al.Cross-talk between signalling pathways and the multidrug resistant protein MDR-1[J].Brit J Cancer,2001,85(8):1175-1184.
[15]KIM MS,SO HS,PARK JS,et al.Hwansodan protects PC12cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein(MAP)kinase pathway[J].Gen Pharmacol,2000,34(4):227-235.
[16]曲文志,李子豪,张云微,等.ghrelin调控ERK信号通路对乳腺癌细胞多药耐药的影响及机制[J].现代肿瘤医学,2017,25(5):687-690.
[17]舒琦瑾,宋央央.南方红豆杉水提物抑制ERK信号通路抗人非小细胞肺癌移植瘤吉非替尼耐药的实验研究[C].北京:全国中医肿瘤学术年会暨岐黄论坛分论坛,2015.
[18]KATAYAMA K,NOGUCHI K,SUGIMOTO Y.Regulations of P-Glycoprotein/ABCB1/MDR1 in Human Cancer Cells[J].New J Sci,2014,2014(5):1-10.
[19]李金霞,马力.沉默PARP-1对乳腺癌细胞MCF-7顺铂耐药的影响[J].中国病理生理杂志,2018,34(2):218-224.
[20]YANDIM MK,APOHAN E,BARAN Y.Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer[J].Cancer Chemother Pharmacol,2013,71(1):13-20.
[21]王倩,邹健,张秀芬,等.GCS通过MEK/ERK通路调控白血病多药耐药细胞凋亡相关基因bcl-2的表达[J].中国病理生理杂志,2015,31(1):114-118.
[22]GUPTA S,BARRETT T,WHITMARSH AJ,et al.Selective interaction of JNK protein kinase isoforms with transcription factors[J].Embo Journal,1996,15(11):2760-2770.
[23]傅应亚,黎友伦.JNK信号通路与细胞凋亡[J].重庆医科大学学报,2014,38(3):281-283.
[24]DAVIES C,TOURNIER C.Exploring the function of the JNK(c-Jun N-terminal kinase)signalling pathway in physiological and pathological processes to design novel therapeutic strategies[J].Biochem Soc Trans,2012,40(1):85-89.
[25]LEE TH,NAM JG,LEE HM,et al.Dexamethasone induces apoptosis of nasal polyp-derived tissue cultures through JNK and p38 MAPK activation[J].Clin Exp Otorhinolar,2014,7(2):112-118.
[26]曲文志,杨蕾,张云微,等.JNK信号通路介导ghrelin对乳腺癌MDA-MB-231细胞耐药蛋白表达的影响[J].实用肿瘤杂志,2016,31(4):340-344.
[27]黄灿,许杜娟,居靖,等.JNK通路介导人肝癌耐药细胞株Bel-7402/FU多药耐药的调控机制[J].肿瘤,2014,34(1):19-25.
[28]严婧,何志旭,栾佐.JNK信号通路受抑制的人白血病K562/ADR细胞对尼洛替尼敏感性[J].山东医药,2017,57(2):14-17.
[29]UEDA K,PASTAN I,GOTTESMAN MM.Isolation and sequence of the promoter region of the human multidrug-resistance(P-glycoprotein)gene[J].J Biol Chem,1987,262(36):17432-17436.
[30]李琦,隋华,刘宣,等.健脾解毒方介导JNK/SAPK信号通路调控人结肠癌细胞多药耐药[J].中华中医药杂志,2012,27(3):731-735.
[31]隋华,周利红,殷佩浩,等.JNK信号通路介导MDR1/P-gp调控人结肠癌多药耐药[J].世界华人消化杂志,2011,19(9):892-898.
[32]周长春,刘芝华,齐军.AP-1和肿瘤的关系研究进展[J].世界华人消化杂志,2006,14(1):1-5.
[33]许雪梅.JNK抑制剂SP600125对人舌鳞癌Tca8113细胞增殖、迁移的影响[D].延边:延边大学,2017.
[34]朱聪,贾秀红,伊英杰,等.龙葵碱对白血病K562/ADR细胞多药耐药性的逆转作用及其分子机制[J].肿瘤,2017,37(12):1276-1281.
[35]LI F,MENG L,ZHOU J,et al.Reversing chemoresistance in cisplatin-resistant human ovarian cancer cells:a role of c-Jun NH2-terminal kinase 1[J].Biochem Bioph Res Co,2005,335(4):1070-1077.
[36]闫美俊.基于JNK信号通路探讨生脉注射液逆转胃癌多药耐药机制研究[D].太原:山西省中医药研究院,2017.
[37]BREWSTER JL,DE TV,DWYER ND,et al.An osmosensing signal transduction pathway in yeast[J].Science,1993,259(5102):1760-1763.
[38]乔静,张秋芳.p38MAPK信号传导通路与肿瘤细胞多药耐药的关系[J].山西医药杂志,2013,42(17):1020-1022.
[39]SANZ V,AROZARENA I,CRESPO P.Distinct carboxy-termini confer divergent characteristics to the mitogen-activated protein kinase p38alpha and its splice isoform Mxi2[J].Febs Lett,2000,474(2-3):169-174.
[40]JABLONSKI EM,MATTOCKS MA,SOKOLOV E,et al.Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma[J].Cancer Lett,2007,250(1):36-46.
[41]JIN W,LU Y,LI Q,et al.Down-regulation of the P-glycoprotein relevant for multidrug resistance by intracellular acidification through the crosstalk of MAPK signaling pathways[J].Int J Biochem Cell Biol,2014,54(8):111-121.
[42]曾少波,兰明银,菅志远,等.乳腺癌细胞耐药过程中p38MAPK活性与细胞凋亡的关系[J].中华乳腺病杂志(电子版),2009,3(1):27-30.
[43]彭铮,史惠蓉,谢娅,等.二甲双胍通过抑制p38MAPK信号通路逆转卵巢癌细胞对顺铂的耐药性[J].肿瘤,2015,35(2):129-138.
[44]马楠楠,郭献灵,王晋,等.胃癌耐药细胞多药耐药基因表达上调中AP-1作用的研究[J].中国肿瘤临床,2008,35(10):582-586.
[45]CHANG CM,LAN KL,HUANG WS,et al.188Re-Liposome can induce mitochondrial autophagy and reverse drug resistance for ovarian cancer:from bench evidence to preliminary clinical proof-of-concept[J].Int J Mol Sci,2017,18(5):903-917.
[46]王泽涛,吕付龙,王劲松.自噬通过p38/c-Jun信号通路促进乳腺癌细胞对他莫昔芬耐药的研究[J].实用肿瘤学杂志,2015,29(1):22-28.
[47]WAGNER EF,NEBREDA AR.Signal integration by JNK and p38 MAPK pathways in cancer development[J].Nat Rev Cancer,2009,9(8):537-549.
[48]BROZOVIC A,FRITZ G,CHRISTMANN M,et al.Long-term activation of SAPK/JNK,p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance[J].Int J Cancer,2004,112(6):974-985.
[49]刘敏,张露蓉,梁国强,等.基于CYP19探讨雷公藤甲素抗ER(+)人乳腺癌MOF-7细胞作用机理[J].南京中医药大学学报,2017,33(4):391-394.
[50]艾俊涛,胡高云,王靓,等.细胞外信号调节激酶及其抑制剂的研究进展[J].中国新药杂志,2013,22(1):43-52.
[51]郝佩琪,安输,杨洋,等.MEK激酶及其抑制剂的研究进展[J].中国细胞生物学学报,2015,37(10):1425-1431.
[52]李鹃利,焦宇,陆涛.小分子RAF激酶抑制剂的临床研究进展[J].广东化工,2015,42(11):110-112.
[53]王国军,刘亚伟,李玉花,等.p38丝裂原活化蛋白激酶抑制剂研究进展[J].生物技术通讯,2009,20(3):399-403.
[54]DUFFY JP,HARRINGTON EM,SALITURO FG,et al.The discovery of VX-745:a novel and selective p38αkinase inhibitor[J].Acs Med Chem Lett,2011,2(10):758-763.
[55]张频捷,朱立新,耿小平.p38 MAPK信号传导通路及其抑制剂的研究现状[J].安徽医药,2010,14(5):596-598.
[56]OZDEMIR C,AKDIS CA.Discontinued drugs in 2006:pulmonary-allergy,dermatological,gastrointestinal and arthritis drugs[J].Expert Opin Investig Drugs,2007,16(9):1327-1344.
[57]陈佳容,邵雷,陈代杰.杂合抗菌药物的研究进展[J].杂合抗菌药物的研究进展[J].中国医药工业杂志,2017,48(9):1233-1246.
[2]SHAO Y,WANG C,HONG Z,et al.Inhibition of p38 mitogenactivated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats[J].J Neurochem,2016,136(5):1096-1105.
[3]刘树人.硫化物应激下单环刺螠MAPK信号通路的功能初探[D].青岛:中国海洋大学,2015.
[4]龚小卫,姜勇.丝裂原活化蛋白激酶(MAPK)生物学功能的结构基础[J].中国生物化学与分子生物学报,2003,19(1):5-11.
[5]WANG Z,HARKINS PC,ULEVITCH RJ,et al.The structure of mitogen-activated protein kinase p38 at 2.1-A resolution[J].Proc Nati Acad Sci USA,1997,94(6):2327-2332.
[6]AKASAKA E,TAKEKOSHI S,HORIKOSHI Y,et al.Protein oxidative damage and heme oxygenase in sunlight-exposed human skin:roles of MAPK responses to oxidative stress[J].Tokai JExp Clin Med,2010,35(4):152-164.
[7]NIX P,HISAMOTO N,MATSUMOTO K,et al.Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways[J].Proc Natl Acad Sci USA,2011,108(26):10738-10743.
[8]JIN W,LU Y,LI Q,et al.Down-regulation of the P-glycoprotein relevant for multidrug resistance by intracellular acidification through the crosstalk of MAPK signaling pathways[J].Int J Biochem Cell Biol,2014,54(8):111-121.
[9]张宗峰,王红丽,时小丁,等.表皮生长因子受体通过MAPK/ERK信号通路调节基质金属蛋白酶1表达的研究[J].国际免疫学杂志,2015,38(6):517-521.
[10]AMANDA T,ZAITUN Z,CAITRN OL,et al.Inhibition of multidrug resistance protein 1(MRP1)improves chemotherapy drug response in primary and recurrent glioblastoma multiforme[J].Front Neurosci,2015,9:218-227.
[11]KATAYAMA K,YOSHIOKA S,TSUKAHARA S,et al.Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein[J].Mol Cancer Ther,2007,6(7):2092-2102.
[12]MENG Q,HE X,XIE G,et al.MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells[J].Oncol Lett,2017,14(3):3089-3095.
[13]MCCUBREY JA,STEELMAN LS,ABRAMS SL,et al.Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance[J].Adv Enzyme Regul,2006,46(1):249-279.
[14]DING S,CHAMBERLAIN M,MCLAREN A,et al.Cross-talk between signalling pathways and the multidrug resistant protein MDR-1[J].Brit J Cancer,2001,85(8):1175-1184.
[15]KIM MS,SO HS,PARK JS,et al.Hwansodan protects PC12cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein(MAP)kinase pathway[J].Gen Pharmacol,2000,34(4):227-235.
[16]曲文志,李子豪,张云微,等.ghrelin调控ERK信号通路对乳腺癌细胞多药耐药的影响及机制[J].现代肿瘤医学,2017,25(5):687-690.
[17]舒琦瑾,宋央央.南方红豆杉水提物抑制ERK信号通路抗人非小细胞肺癌移植瘤吉非替尼耐药的实验研究[C].北京:全国中医肿瘤学术年会暨岐黄论坛分论坛,2015.
[18]KATAYAMA K,NOGUCHI K,SUGIMOTO Y.Regulations of P-Glycoprotein/ABCB1/MDR1 in Human Cancer Cells[J].New J Sci,2014,2014(5):1-10.
[19]李金霞,马力.沉默PARP-1对乳腺癌细胞MCF-7顺铂耐药的影响[J].中国病理生理杂志,2018,34(2):218-224.
[20]YANDIM MK,APOHAN E,BARAN Y.Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer[J].Cancer Chemother Pharmacol,2013,71(1):13-20.
[21]王倩,邹健,张秀芬,等.GCS通过MEK/ERK通路调控白血病多药耐药细胞凋亡相关基因bcl-2的表达[J].中国病理生理杂志,2015,31(1):114-118.
[22]GUPTA S,BARRETT T,WHITMARSH AJ,et al.Selective interaction of JNK protein kinase isoforms with transcription factors[J].Embo Journal,1996,15(11):2760-2770.
[23]傅应亚,黎友伦.JNK信号通路与细胞凋亡[J].重庆医科大学学报,2014,38(3):281-283.
[24]DAVIES C,TOURNIER C.Exploring the function of the JNK(c-Jun N-terminal kinase)signalling pathway in physiological and pathological processes to design novel therapeutic strategies[J].Biochem Soc Trans,2012,40(1):85-89.
[25]LEE TH,NAM JG,LEE HM,et al.Dexamethasone induces apoptosis of nasal polyp-derived tissue cultures through JNK and p38 MAPK activation[J].Clin Exp Otorhinolar,2014,7(2):112-118.
[26]曲文志,杨蕾,张云微,等.JNK信号通路介导ghrelin对乳腺癌MDA-MB-231细胞耐药蛋白表达的影响[J].实用肿瘤杂志,2016,31(4):340-344.
[27]黄灿,许杜娟,居靖,等.JNK通路介导人肝癌耐药细胞株Bel-7402/FU多药耐药的调控机制[J].肿瘤,2014,34(1):19-25.
[28]严婧,何志旭,栾佐.JNK信号通路受抑制的人白血病K562/ADR细胞对尼洛替尼敏感性[J].山东医药,2017,57(2):14-17.
[29]UEDA K,PASTAN I,GOTTESMAN MM.Isolation and sequence of the promoter region of the human multidrug-resistance(P-glycoprotein)gene[J].J Biol Chem,1987,262(36):17432-17436.
[30]李琦,隋华,刘宣,等.健脾解毒方介导JNK/SAPK信号通路调控人结肠癌细胞多药耐药[J].中华中医药杂志,2012,27(3):731-735.
[31]隋华,周利红,殷佩浩,等.JNK信号通路介导MDR1/P-gp调控人结肠癌多药耐药[J].世界华人消化杂志,2011,19(9):892-898.
[32]周长春,刘芝华,齐军.AP-1和肿瘤的关系研究进展[J].世界华人消化杂志,2006,14(1):1-5.
[33]许雪梅.JNK抑制剂SP600125对人舌鳞癌Tca8113细胞增殖、迁移的影响[D].延边:延边大学,2017.
[34]朱聪,贾秀红,伊英杰,等.龙葵碱对白血病K562/ADR细胞多药耐药性的逆转作用及其分子机制[J].肿瘤,2017,37(12):1276-1281.
[35]LI F,MENG L,ZHOU J,et al.Reversing chemoresistance in cisplatin-resistant human ovarian cancer cells:a role of c-Jun NH2-terminal kinase 1[J].Biochem Bioph Res Co,2005,335(4):1070-1077.
[36]闫美俊.基于JNK信号通路探讨生脉注射液逆转胃癌多药耐药机制研究[D].太原:山西省中医药研究院,2017.
[37]BREWSTER JL,DE TV,DWYER ND,et al.An osmosensing signal transduction pathway in yeast[J].Science,1993,259(5102):1760-1763.
[38]乔静,张秋芳.p38MAPK信号传导通路与肿瘤细胞多药耐药的关系[J].山西医药杂志,2013,42(17):1020-1022.
[39]SANZ V,AROZARENA I,CRESPO P.Distinct carboxy-termini confer divergent characteristics to the mitogen-activated protein kinase p38alpha and its splice isoform Mxi2[J].Febs Lett,2000,474(2-3):169-174.
[40]JABLONSKI EM,MATTOCKS MA,SOKOLOV E,et al.Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma[J].Cancer Lett,2007,250(1):36-46.
[41]JIN W,LU Y,LI Q,et al.Down-regulation of the P-glycoprotein relevant for multidrug resistance by intracellular acidification through the crosstalk of MAPK signaling pathways[J].Int J Biochem Cell Biol,2014,54(8):111-121.
[42]曾少波,兰明银,菅志远,等.乳腺癌细胞耐药过程中p38MAPK活性与细胞凋亡的关系[J].中华乳腺病杂志(电子版),2009,3(1):27-30.
[43]彭铮,史惠蓉,谢娅,等.二甲双胍通过抑制p38MAPK信号通路逆转卵巢癌细胞对顺铂的耐药性[J].肿瘤,2015,35(2):129-138.
[44]马楠楠,郭献灵,王晋,等.胃癌耐药细胞多药耐药基因表达上调中AP-1作用的研究[J].中国肿瘤临床,2008,35(10):582-586.
[45]CHANG CM,LAN KL,HUANG WS,et al.188Re-Liposome can induce mitochondrial autophagy and reverse drug resistance for ovarian cancer:from bench evidence to preliminary clinical proof-of-concept[J].Int J Mol Sci,2017,18(5):903-917.
[46]王泽涛,吕付龙,王劲松.自噬通过p38/c-Jun信号通路促进乳腺癌细胞对他莫昔芬耐药的研究[J].实用肿瘤学杂志,2015,29(1):22-28.
[47]WAGNER EF,NEBREDA AR.Signal integration by JNK and p38 MAPK pathways in cancer development[J].Nat Rev Cancer,2009,9(8):537-549.
[48]BROZOVIC A,FRITZ G,CHRISTMANN M,et al.Long-term activation of SAPK/JNK,p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance[J].Int J Cancer,2004,112(6):974-985.
[49]刘敏,张露蓉,梁国强,等.基于CYP19探讨雷公藤甲素抗ER(+)人乳腺癌MOF-7细胞作用机理[J].南京中医药大学学报,2017,33(4):391-394.
[50]艾俊涛,胡高云,王靓,等.细胞外信号调节激酶及其抑制剂的研究进展[J].中国新药杂志,2013,22(1):43-52.
[51]郝佩琪,安输,杨洋,等.MEK激酶及其抑制剂的研究进展[J].中国细胞生物学学报,2015,37(10):1425-1431.
[52]李鹃利,焦宇,陆涛.小分子RAF激酶抑制剂的临床研究进展[J].广东化工,2015,42(11):110-112.
[53]王国军,刘亚伟,李玉花,等.p38丝裂原活化蛋白激酶抑制剂研究进展[J].生物技术通讯,2009,20(3):399-403.
[54]DUFFY JP,HARRINGTON EM,SALITURO FG,et al.The discovery of VX-745:a novel and selective p38αkinase inhibitor[J].Acs Med Chem Lett,2011,2(10):758-763.
[55]张频捷,朱立新,耿小平.p38 MAPK信号传导通路及其抑制剂的研究现状[J].安徽医药,2010,14(5):596-598.
[56]OZDEMIR C,AKDIS CA.Discontinued drugs in 2006:pulmonary-allergy,dermatological,gastrointestinal and arthritis drugs[J].Expert Opin Investig Drugs,2007,16(9):1327-1344.
[57]陈佳容,邵雷,陈代杰.杂合抗菌药物的研究进展[J].杂合抗菌药物的研究进展[J].中国医药工业杂志,2017,48(9):1233-1246.