摘要
背景和目的:博安霉素(Boanmycin,BAM)是博来霉素的A6组分,临床研究表明对多种肿瘤有效。趋化肽可吸引与激活白细胞(含巨噬细胞),使其对肿瘤生长、侵袭与转移过程产生一定的影响。本研究探讨BAM和趋化肽fMLP(N-formyl-methionyl-leucyl-phenylalanine,CHO-Met-Ile-Phe)联合抗肿瘤作用。方法:体外采用MTT法测定BAM和fMLP联合对肿瘤细胞的细胞毒作用,尤其是巨噬细胞存在时的作用。体内实验以小鼠移植性肝癌H22模型观察BAM和fMLP联合抗肿瘤作用。结果:体外实验,BAM与fMLP联合对肿瘤细胞没有协同作用,但BAM10μg/ml、30μg/ml和100μg/ml与fMLP20μg/ml联合在加入巨噬细胞后对肿瘤细胞有显著协同作用。体内实验时,fMLP1mg/mouse为瘤周给药×3,fMLP无显著抗肿瘤作用。BAM和fMLP合用时设计了3个实验:(1)肿瘤接种后24h开始治疗,BAM为瘤周给药×3,BAM0.5mg/kg在13天的抑瘤率为26.6%,合用fMLP后为64.7%,P<0.05,CDI值为0.36,有显著协同作用。(2)肿瘤接种后24h开始治疗,BAM为腹腔给药×3,BAM1mg/kg组肿瘤生长较快,合用fMLP后生长缓慢。在14天的抑瘤率为11%,合用fMLP后为70.6%,P<0.05,CDI为0.42,有显著协同作用。(3)肿瘤接种后96h开始治疗,BAM腹腔给药×3,BAM1mg/kg组肿瘤生长较快,合用fMLP后生长缓慢。在13天的抑瘤?
Background &Objective:Boanmycin(BAM),a single A6component of the bleomycin complex,is effective against a panel of cancers in clinical trials.Chemotactic pep tide can activate and attract leukocytes and macrophages that may interfere with the process o f tumor growth,invasion,and metastasis.This study was designed to inve stigate the antitumor activity of BAM in combination with chemotactic peptide N-formyl-methionyl-leucyl-phenylalan ine(fMLP).Methods :Cytotoxicity of BAM and fMLP to tumor cells was determined by MTT assay,particularly in presence of macrophages.Therapeutic effect wa s evaluated by using the model of subcutaneously transplanted hepatoma 22in mice.Results:In vitro experiment showed that BAM a nd fMLP had no synergism in cytotoxic ity to tumor cells.However,in the presence of macrophages,BAM at concentrations of 10,30,and 100μg /ml in combination with fMLP 20μg /ml displayed synergistic effect in cytotoxicity.In all in vivo experiments,fMLP adm inistered peritumorally 3times at t he dose of 1mg /mouse showed no significant growth i nhibition.Three settings of BAM and fMLP combination included:(1)BAM,administered peritumorally ×3,was started 24h after tumor inoculation.BAM(0.5mg /kg)alone and BAM-fMLP combination inhi bited the growth of hepatoma 22by 26.6%and64.7%,respectively(P<0.05,CDI =0.36)on day 13.(2)BAM,administered ip ×3,was started 24h a fter tumor inoculation.The tumor growth in BAM(1mg /kg)group was faster than that in BAM-fMLP combination group.On day 14,BAM(1mg /kg)alone and BAM-fMLP combination supp ressed the tumor growth by 11%and 70.6%,respectively(P<0.05,CDI =0.42).(3)BAM,administered ip ×3,was started96h after tumor inoculation.The tumor g rowth in BAM(1mg /kg)group was faster than that in BAM-fML P combination group.On day 13,BAM(1mg /kg)alone and BAM-fMLP combination suppressed the tumor growth by 38.2%and 77.1%,respectively(P<0.05,CDI =0.51).As shown in all in vivo experimental settings,antitumor effect of BAM in combination with fMLP was much more p otent than that of
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2002年第8期828-832,共5页
Chinese Journal of Cancer
基金
国家重点基础性研究973项目(G1998051104)
