苏拉明抗肿瘤作用研究进展
张居馨
( 天津医药科学研究所 生物技术室 天津300070 )
[摘要] 苏拉明是一个用于治疗锥虫和/或盘尾丝虫感染的抗寄生虫药。近些年研究发现苏拉明对肿瘤细胞增殖、浸润、转移等有一定的抑制作用。体内外研究证实苏拉明对多种恶性肿瘤有抗肿瘤活性。本文综述了近二十年来苏拉明抗肿瘤研究的进展，简述了苏拉明的理化特性、吸收分布，重点叙述了苏拉明抗肿瘤作用机制以及临床应用。
[关键词] 苏拉明；抗肿瘤作用机制；临床应用
THE NEW PROGRESS OF THE RESEARCH ON THE ANTITUMOR EFFECTS OF SURAMIN
Zhang Ju-xin
, 百拇医药 Laboratory of Biotechnique, Tianjin Medicine & Pharmaceutical Institute
Tianjin ( 300070 )
[Abstract] Suramin has long been used to treat human trypanosomiasis and onchocerciasis, but since the recent years has received attention as an antitumor drug which has some inhibitory effect on the proliferation ,invasion and metastasis of some malignant tumor cells in vitro and in vivo. The new progress of the research on the antitumor effect of suramin was reviewed, the physiochemical characteristics, and its pharmacokinetics were described, the antitumor effect and clinical application of this drug were emphasized.
, 百拇医药
[Key words] suramin ; antitumor effect; clinical application.
[作者简介] 张居馨(1949—)，女，研究员，从事药理、免疫、细胞学研究。联系电话：(022)23358826—3019，Email: tjimps@publicltpt.tj 。
[ 参考文献 ]
[1] Mitsuya H, Popovic M, Yarchoan R, et al, Suramin protection of T cell in vitro against infectivity and cytopathic effect of HTLV-III[J]. Science (Washington DC) , 1984, 226: 172-174
[2] Cheson B,Levine A, Mildvan D, Kaplan L, et al, Suramin therapy in AIDS and related disorders[J]. JAMA, 1987,258:1347-1351
, 百拇医药
[3] De Clercq E. Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses[J]. Cancer lett, 1979, 8: 9-22
[4] Walther MM, Figg WO, Linehtan WM. Intravesical suramin: a novel agent for the treatment of superficial transitional-cell carcinoma of the bladder[J]. World J Urol, 1996, 14:58.
[5] Sklar GN, Eddy HA, Jacobs SC, et al, Combined antitumor effect of suramin plus irradiation in human prostate cancer cell: the role of apoptosis[J]. J Urol, 1993, 150:1526.
, 百拇医药
[6] Scher H, Jodrell D, Iversen J, et al, Use of adaptive control with feedbalk to individualize suramin dosing[J]. Cancer Res, 1992, 52: 64-70
[7] Williams L, Tremble P, Lavin M, et al, Platelet-derived growth factor receptors from a high affinity state in membrane preparations[J]. J Biol Chem, 1984, 259: 5287-5294
[8] Walz T, Abdia A, Wingren S, et al, Suramin inhibits growth of human osteosarcoma xenografts in nude mice[J]. Cancer Res, 1991, 51: 3585-3589
, 百拇医药
[9] Lawrence JB, Conover CA, Haddad TC, et al, Evaluation of continous infusion Suramin in
metastatic breast cancer : impact on plasma levels of insulin –like growth Factors (IGFs) and
IGF-binding proteins[J]. Clin Cancer Res, 1997, 3(10): 1713-1720
[10] Minniti CP，Maggi M，Helman LJ，et al, Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the Insulin-like growth factor II autocrine growth loop[J]. Cancer Res , 1992 ,Apr 1;52(7):1830-5
, 百拇医药
[11] Pollak M, and Richard M. Suramin blockade of in insulin-like growth factor-I stimulated proliferation of human osteosarcoma cells[J]. J Natl Cancer Inst, 1990, 82: 1349-1352
[12] Mills G, Zhang N, May C, et al, Suramin prevents binding of interleukin II to its cell surface receptor: a possible mechanisim for immunosuppression[J]. Cancer Res, 1990, 50: 3036-3642
[13] Ono K, Nakane H, Fukushima M, Differential inhibition of various deoxyribonucleic and ribonucleic acid polymerases by suramin[J]. Eur J Biochem, 1988, 172: 349-353
, 百拇医药
[14] Moriyama Y and Nelson N. Inhibition of vacuolar H+_ATPase by fusidic acid and suramin[J]. F E B S lett, 1988, 257: 2664-2673
[15] 李安太, 王天铎. 苏洛明抗肿瘤作用[J]. 国外医学肿瘤分册1992，19(1)：15-20
[16] Folkman J and Shing Y. Angiogenesis [J], J Biol Chem, 1992, 267: 10931-10934
[17] Takano S, Gately S, Mary E, et al, Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator[J]. Cancer Res, 1994, 54: 2654—2660
, http://www.100md.com
[18] Gasparini G. The rationale and future potential of angiogenesis inhibitors in neoplasia[J]. Drugs, 1999, 58 (1): 17-38
[19] Marusuka K, Hasui Y, Asada Y, et al, Effects of suramin on metastatic ability, proliferation, and production of urokinasetype plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12c-PM6[J]. Clin Exp Metastasis 1995,13(2):116-122
[20] Vignon F, Prebois C, Rochefort H. Inhibition of breast cancer growth by suramin[J]. J Natl Cancer Inst, 1992, 84 (1): 38-42
, 百拇医药
[21] Qin LX, Tang ZY, Li XM, et al, Effect of antiangiogenic agents on experimental animal models of hepatocellular carcinoma[J]. Ann Acad Med Singapore, 1999, 28(1): 147-151
[22] 刘暌 雷霆 张龙等，肽类生长因子及苏拉明对体外培养人脑膜瘤细胞生长的影响，[J] 中华实验外科杂志，1999，16(5)：432-433
[23] R. SHTN Y, NAOMOTO Y, KAMIKA WA， et al， 苏拉明在体外和体内对人类食管癌细胞的作用，[J] 斯堪的那维亚胃肠病学杂志，1997，11(4)：251-256
[24] 孙西钊，郭宏骞; 苏拉明抗前列腺癌作用。国外医学肿瘤分册1995，22(5)：296-298
, http://www.100md.com
[25] Stein CA. Suramin: novel antineoplastic agent with multiple potential mechanisms of action[J]. Cancer Res, 1993, 53: 2239-2248
[26] 杨宝龙, 顾方六, 丁义, 等， X线和苏拉明联合应用诱导肾癌GRC-1细胞凋亡的研究，[J].中华泌尿外科杂志，1997，18(9)：518-521
[27]李晓明，张秀荣. 苏拉明对人肝癌在裸鼠体内生长和转移的抑制作用, [J] 中华实验外科杂志，1998，15(1)3-4
[28]Ben-Baruch N, Reinhold wc, Alexandrova N, et al, C-mycDown-regulation in suramin-treated
, 百拇医药
HL60 cells precedes growth inhibition but not tigger differentiation[J]. Mol Pharmacol .1994,46(1): 73-8
[29] Forgne-Lafille ME, Coudray AM, Breant B, et al, Poliferation of the human colon carcinoma cell line HT29 autocrine growth and deregulated expression of the c-myc oncogene[J], Cancer Res , 1989. Dec 1:49 (23) 6566-71
[30] Lara PN Jr and Meyers FJ. Treatment option in androgen- independent prostate cancer[J].
, http://www.100md.com
Cancer Invest, 1999, 17(2) : 137-144
[31] Falcone A, Pfamer E, Ciancic, et al, Suramin in patients with metastatic colorectal cancerpretreated with fluoropyrimidine-based chemotherapy A phase II study[J]. Cancer, 1995, 75 (2): 440-443
[32] Rosen PJ, Mendoza EF, Landaw EM, et al, Suramin in hormone-refractory metastatic prostate cancer: a drug with liminited efficacy[J]. J Clin Oncol, 1996, 14 (5): 1626-1636
, 百拇医药
[33] Kobayashi K, Weiss RE, Vogelzang NJ, et al, Mineralocorticoid insufficiency due to suramin therapy.[J]. Cancer 1996 ,78(11):2411-2420
[34] Tisdale JF, Figg WD, Read E, et al, Severe thrombocy topenia in patients treated with Suramin: evidence for an immune mechanism in one[J]. AM J Hematol, 1996, 51(2): 152-157
[35] Chaudhry V, Eisenberger MA, Sinibaldi VJ, et al, A prospective study of suramin-induced peripheral neuropathy. [J]. Brain 1996 Dec;119( 6):2039-2052, 百拇医药
( 天津医药科学研究所 生物技术室 天津300070 )
[摘要] 苏拉明是一个用于治疗锥虫和/或盘尾丝虫感染的抗寄生虫药。近些年研究发现苏拉明对肿瘤细胞增殖、浸润、转移等有一定的抑制作用。体内外研究证实苏拉明对多种恶性肿瘤有抗肿瘤活性。本文综述了近二十年来苏拉明抗肿瘤研究的进展，简述了苏拉明的理化特性、吸收分布，重点叙述了苏拉明抗肿瘤作用机制以及临床应用。
[关键词] 苏拉明；抗肿瘤作用机制；临床应用
THE NEW PROGRESS OF THE RESEARCH ON THE ANTITUMOR EFFECTS OF SURAMIN
Zhang Ju-xin
, 百拇医药 Laboratory of Biotechnique, Tianjin Medicine & Pharmaceutical Institute
Tianjin ( 300070 )
[Abstract] Suramin has long been used to treat human trypanosomiasis and onchocerciasis, but since the recent years has received attention as an antitumor drug which has some inhibitory effect on the proliferation ,invasion and metastasis of some malignant tumor cells in vitro and in vivo. The new progress of the research on the antitumor effect of suramin was reviewed, the physiochemical characteristics, and its pharmacokinetics were described, the antitumor effect and clinical application of this drug were emphasized.
, 百拇医药
[Key words] suramin ; antitumor effect; clinical application.
[作者简介] 张居馨(1949—)，女，研究员，从事药理、免疫、细胞学研究。联系电话：(022)23358826—3019，Email: tjimps@publicltpt.tj 。
[ 参考文献 ]
[1] Mitsuya H, Popovic M, Yarchoan R, et al, Suramin protection of T cell in vitro against infectivity and cytopathic effect of HTLV-III[J]. Science (Washington DC) , 1984, 226: 172-174
[2] Cheson B,Levine A, Mildvan D, Kaplan L, et al, Suramin therapy in AIDS and related disorders[J]. JAMA, 1987,258:1347-1351
, 百拇医药
[3] De Clercq E. Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses[J]. Cancer lett, 1979, 8: 9-22
[4] Walther MM, Figg WO, Linehtan WM. Intravesical suramin: a novel agent for the treatment of superficial transitional-cell carcinoma of the bladder[J]. World J Urol, 1996, 14:58.
[5] Sklar GN, Eddy HA, Jacobs SC, et al, Combined antitumor effect of suramin plus irradiation in human prostate cancer cell: the role of apoptosis[J]. J Urol, 1993, 150:1526.
, 百拇医药
[6] Scher H, Jodrell D, Iversen J, et al, Use of adaptive control with feedbalk to individualize suramin dosing[J]. Cancer Res, 1992, 52: 64-70
[7] Williams L, Tremble P, Lavin M, et al, Platelet-derived growth factor receptors from a high affinity state in membrane preparations[J]. J Biol Chem, 1984, 259: 5287-5294
[8] Walz T, Abdia A, Wingren S, et al, Suramin inhibits growth of human osteosarcoma xenografts in nude mice[J]. Cancer Res, 1991, 51: 3585-3589
, 百拇医药
[9] Lawrence JB, Conover CA, Haddad TC, et al, Evaluation of continous infusion Suramin in
metastatic breast cancer : impact on plasma levels of insulin –like growth Factors (IGFs) and
IGF-binding proteins[J]. Clin Cancer Res, 1997, 3(10): 1713-1720
[10] Minniti CP，Maggi M，Helman LJ，et al, Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the Insulin-like growth factor II autocrine growth loop[J]. Cancer Res , 1992 ,Apr 1;52(7):1830-5
, 百拇医药
[11] Pollak M, and Richard M. Suramin blockade of in insulin-like growth factor-I stimulated proliferation of human osteosarcoma cells[J]. J Natl Cancer Inst, 1990, 82: 1349-1352
[12] Mills G, Zhang N, May C, et al, Suramin prevents binding of interleukin II to its cell surface receptor: a possible mechanisim for immunosuppression[J]. Cancer Res, 1990, 50: 3036-3642
[13] Ono K, Nakane H, Fukushima M, Differential inhibition of various deoxyribonucleic and ribonucleic acid polymerases by suramin[J]. Eur J Biochem, 1988, 172: 349-353
, 百拇医药
[14] Moriyama Y and Nelson N. Inhibition of vacuolar H+_ATPase by fusidic acid and suramin[J]. F E B S lett, 1988, 257: 2664-2673
[15] 李安太, 王天铎. 苏洛明抗肿瘤作用[J]. 国外医学肿瘤分册1992，19(1)：15-20
[16] Folkman J and Shing Y. Angiogenesis [J], J Biol Chem, 1992, 267: 10931-10934
[17] Takano S, Gately S, Mary E, et al, Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator[J]. Cancer Res, 1994, 54: 2654—2660
, http://www.100md.com
[18] Gasparini G. The rationale and future potential of angiogenesis inhibitors in neoplasia[J]. Drugs, 1999, 58 (1): 17-38
[19] Marusuka K, Hasui Y, Asada Y, et al, Effects of suramin on metastatic ability, proliferation, and production of urokinasetype plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12c-PM6[J]. Clin Exp Metastasis 1995,13(2):116-122
[20] Vignon F, Prebois C, Rochefort H. Inhibition of breast cancer growth by suramin[J]. J Natl Cancer Inst, 1992, 84 (1): 38-42
, 百拇医药
[21] Qin LX, Tang ZY, Li XM, et al, Effect of antiangiogenic agents on experimental animal models of hepatocellular carcinoma[J]. Ann Acad Med Singapore, 1999, 28(1): 147-151
[22] 刘暌 雷霆 张龙等，肽类生长因子及苏拉明对体外培养人脑膜瘤细胞生长的影响，[J] 中华实验外科杂志，1999，16(5)：432-433
[23] R. SHTN Y, NAOMOTO Y, KAMIKA WA， et al， 苏拉明在体外和体内对人类食管癌细胞的作用，[J] 斯堪的那维亚胃肠病学杂志，1997，11(4)：251-256
[24] 孙西钊，郭宏骞; 苏拉明抗前列腺癌作用。国外医学肿瘤分册1995，22(5)：296-298
, http://www.100md.com
[25] Stein CA. Suramin: novel antineoplastic agent with multiple potential mechanisms of action[J]. Cancer Res, 1993, 53: 2239-2248
[26] 杨宝龙, 顾方六, 丁义, 等， X线和苏拉明联合应用诱导肾癌GRC-1细胞凋亡的研究，[J].中华泌尿外科杂志，1997，18(9)：518-521
[27]李晓明，张秀荣. 苏拉明对人肝癌在裸鼠体内生长和转移的抑制作用, [J] 中华实验外科杂志，1998，15(1)3-4
[28]Ben-Baruch N, Reinhold wc, Alexandrova N, et al, C-mycDown-regulation in suramin-treated
, 百拇医药
HL60 cells precedes growth inhibition but not tigger differentiation[J]. Mol Pharmacol .1994,46(1): 73-8
[29] Forgne-Lafille ME, Coudray AM, Breant B, et al, Poliferation of the human colon carcinoma cell line HT29 autocrine growth and deregulated expression of the c-myc oncogene[J], Cancer Res , 1989. Dec 1:49 (23) 6566-71
[30] Lara PN Jr and Meyers FJ. Treatment option in androgen- independent prostate cancer[J].
, http://www.100md.com
Cancer Invest, 1999, 17(2) : 137-144
[31] Falcone A, Pfamer E, Ciancic, et al, Suramin in patients with metastatic colorectal cancerpretreated with fluoropyrimidine-based chemotherapy A phase II study[J]. Cancer, 1995, 75 (2): 440-443
[32] Rosen PJ, Mendoza EF, Landaw EM, et al, Suramin in hormone-refractory metastatic prostate cancer: a drug with liminited efficacy[J]. J Clin Oncol, 1996, 14 (5): 1626-1636
, 百拇医药
[33] Kobayashi K, Weiss RE, Vogelzang NJ, et al, Mineralocorticoid insufficiency due to suramin therapy.[J]. Cancer 1996 ,78(11):2411-2420
[34] Tisdale JF, Figg WD, Read E, et al, Severe thrombocy topenia in patients treated with Suramin: evidence for an immune mechanism in one[J]. AM J Hematol, 1996, 51(2): 152-157
[35] Chaudhry V, Eisenberger MA, Sinibaldi VJ, et al, A prospective study of suramin-induced peripheral neuropathy. [J]. Brain 1996 Dec;119( 6):2039-2052, 百拇医药