力达霉素辅基蛋白与人体乳腺癌结合作用的组织芯片研究  

Binding capability of lidamycin apoprotein to human breast cancer detected by tissue microarrays

作　　者：蔡琳[1,2] 高瑞娟[1] 郭效忠[3] 李毅[1] 甄永苏[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050 [2]温州医学院药学院,浙江温州325035 [3]沧州市中心医院,河北沧州061000

出　　处：《药学学报》2010年第5期582-588,共7页Acta Pharmaceutica Sinica

基　　金：“重大新药创制”国家科技重大专项课题(2009ZX09103-136)

摘　　要：观察力达霉素辅基蛋白LDP与乳腺癌及乳腺正常组织的结合作用,并进一步研究与VEGF和HER2在乳腺癌中表达的相关性。采用免疫组织化学方法和结合组织芯片技术,研究LDP与乳腺癌组织及相应正常乳腺组织的结合;进而在多种病理类型乳腺癌组织芯片上,平行检测VEGF和HER2的表达,并与LDP和乳腺癌组织的结合进行比较,分析相关性。应用免疫细胞化学方法观察LDP与人乳腺癌MCF-7细胞的结合作用。结果显示,在乳腺癌及相应正常乳腺组织芯片上,LDP与乳腺癌组织结合的阳性率为73.2%(30/41),明显高于正常乳腺组织48.3%(15/31),两者有显著差异(χ2=4.63,P<0.05)。在多种病理类型乳腺癌组织芯片上,考察LDP与乳腺癌结合阳性的病例表明,VEGF表达阳性率为88.9%(48/54),两者呈正相关(P<0.001,r=0.389);HER2表达阳性率为84.0%(42/54),两者呈正相关(P<0.01,r=0.287)。激光共聚焦显微镜检测表明,LDP可与人乳腺癌细胞MCF-7结合。上述结果表明,LDP可与乳腺癌组织结合,并与VEGF、HER2在乳腺癌组织中的表达有相关性。LDP与乳腺癌组织结合作用的研究,有可能为力达霉素与其他靶向药物的联合用药提供依据;也提示LDP作为肿瘤靶向药物导向载体的可能性。This study is to investigate the binding capability of lidamycin apoprotein （LDP）,an enediyne-associated apoprotein of the chromoprotein antitumor antibiotic family,to human breast cancer and normal tissues,the correlation of LDP binding capability to human breast cancer tissues and the expression of tumor therapeutic targets such as VEGF and HER2.In this study,the binding capability of LDP to human breast cancer tissues was detected with tissue microarray.The correlation study of LDP binding capability to human breast tumor tissues and relevant therapeutic targets was performed on breast cancer tissue microarrays.Immunocytochemical examination was used to detect the binding capability of LDP to human breast carcinoma MCF-7 cells.As a result,tissue microarray showed that LDP staining of 73.2% （30/41） of breast cancer tissues was positive,whereas that of 48.3% （15/31） of the adjacent normal breast specimens was positive.The difference between the tumor and normal samples was significant （χ^2 = 4.63,P 0.05）.LDP immunoreactivity in breast cancer correlated significantly with the overexpression of VEGF and HER2 （P 0.001 and 0.01,r = 0.389 and 0.287,respectively）.Determined with confocal immunofluorescent analysis,LDP showed the binding capability to mammary carcinoma MCF-7 cells.It is demonstrated that LDP can bind to human breast cancer tissues and there is significant difference between the breast cancer tissues and the corresponding normal tissues.Notably,the binding reactivity shows positive correlation with the expression of VEGF and HER2 in breast carcinoma tissues.The results imply that LDP may have a potential use as targeting drug carrier in the research and developmont of new anticancer therapeutics.This study may provide reference for drug combination of LDM and other therapeutic agents.

关 键 词：力达霉素 乳腺癌 免疫组织化学 VEGF HER2 

分 类 号：R963[医药卫生—微生物与生化药学]