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EFFECT AND MECHANISM OF SECURININE ON SYNAPTIC TRANSMISSION IN THE DENTATE GYRUS OF ANESTHETIZED RATSSYNERGISTIC EFFECTS OF GELDANAMYCIN AND ANTITUMOR DRUGS

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Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 8

DOI:: 10.3321/j.issn:0513-4870.2001.08.003

Key Word:: 格尔德霉素;顺铂;丝裂霉素C;生化调节剂;肿瘤联合化疗

Abstract：目的研究格尔德霉素(Geldanamycin,GDM)对人肝癌BEL-7402细胞周期的影响及顺铂和丝裂霉素C等药物联用GDM后的体外体内抗肿瘤作用.方法用MTT法检测药物对肝癌BEL-7402细胞的生长抑制作用;流式细胞术分析细胞周期;小鼠移植性肝癌22模型研究药物的体内抗肿瘤作用.结果 MTT法测得GDM对BEL-7402细胞的生长抑制作用IC50为0.28 μmol*L-1.GDM 0.1,1.0和10 μmol*L-1处理BEL-7402细胞,引起S期细胞比例下降和G2/M期的明显阻断.在较低浓度,GDM 0.1 μmol*L-1和0.2 μmol*L-1均增强一系列化疗药物包括顺铂、丝裂霉素C、阿霉素和阿糖胞苷对BEL-7402细胞的细胞毒作用.小鼠移植肝癌22模型中,GDM 0.38 mg*kg-1增强顺铂和丝裂霉素C的抗肿瘤作用.协同作用十分显著,CDI<0.7.结论这些结果提示GDM作为以抑制热休克蛋白90(Hsp90)功能为靶点的生化调节剂可能应用于肿瘤联合化疗的前景.

Reference

[1]A J, McIlwrath,V G, Brunton,R, Brown.Cell-cycle arrest and p53 accumulation induced by geldanamycin in human ovarian tumour cells.[J].1996,37(5).
[2]W G, An,R C, Schnur,L, Neckers,etc.Depletion of p185erbB2, Raf-1 and mutant p53 proteins by geldanamycin derivatives correlates with antiproliferative activity.[J].1997,40(1).
[3]Prohaszka Z,Nardai G,Schnaider T,etc.The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review.[J].1998,79(2).
[4]J, Su,Y S, Zhen,C Q, Qi,etc.[A fungus-derived novel nucleoside transport inhibitor potentiates the activity of antitumor drugs].[J].1994,29(9).
[5]L H, Pearl,C, Prodromou.Structure and in vivo function of Hsp90.[J].2000,10(1).
[6]Brechbiel JK,Mandler R,Brechbiel MW,etc.Synthesis and evaluation of antiproliferative activity of a geldanamycin-Herceptin immunoconjugate.[J].2000,10(10).
[7]S E, Conroy,D S, Latchman.Do heat shock proteins have a role in breast cancer?[J].1996,74(5).
[8]Lopez-Maderuelo,MD,Fernandez-Renart,M,Moratilla,C,etc.Opposite effects of the Hsp90 inhibitor Geldanamycin: induction of apoptosis in PC12, and differentiation in N2A cells.[J].2001,490(1/2).
[9]姜晓峰,甄永苏.大黄素逆转肿瘤细胞多药抗药性的作用[J].1999,(3).
[10]Shah M Khan,Rush H Oliver,Lisa M Dauffenbach,etc.Depletion of Raf-1 protooncogene by geldanamycin causes apoptosis in human luteinized granulosa cells[J].2000,74(2).
[11]J, Carmichael,W G, DeGraff,A F, Gazdar,etc.Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing.[J].1987,47(4).
[12]Y S, Zhen,T, Taniki,G, Weber.Azidothymidine and dipyridamole as biochemical response modifiers: synergism with methotrexate and 5-fluorouracil in human colon and pancreatic carcinoma cells.[J].1992,4(2).
[13]Tikhomirov O,Carpenter G.Geldanamycin induces ErbB-2 degradation by proteolytic fragmentation.[J].2000,275(34).
[14]L, Whitesell,E G, Mimnaugh,B, De Costa,etc.Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.[J].1994,91(18).
[15]DEBOER C.,MEULMAN P.A.,WNUK R.J.,etc.Geldanamycin, a New Antibiotic[J].1970.
[16]L, Zhang,M C, Hung.Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin.[J].1996,12(3).
[17]Neckers L,Mimnaugh E,Schulte TW.Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity.[J].1999,17(4).
[18]M, Yano,Z, Naito,S, Tanaka,etc.Expression and roles of heat shock proteins in human breast cancer.[J].1996,87(9).
[19]Marina Ferrarini,Silvia Heltai,M. Raffaella Zocchi,etc.Unusual expression and localization of heat-shock proteins in human tumor cells[J].1992,51(4).
[20]L, Zhang,Y K, Lau,W, Xia,etc.Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel.[J].1999,5(2).
[21]Hong Ro Kim,Chang Hoon Lee,Yung Hyun Choi.Geldanamycin induces cell cycle arrest in K562 erythroleukemic cells[J].1999,48(4).
[22]Scheibel T,Buchner J.The Hsp90 complex--a super-chaperone machine as a novel drug target.[J].1998,56(6).
[23]Laura M. Vargas-Roig,Francisco E. Gago,Olga Tello,etc.Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy[J].1998,79(5).
[24]S S, Cao,Y S, Zhen.Potentiation of antimetabolite antitumor activity in vivo by dipyridamole and amphotericin B.[J].1989,24(3).