乳腺癌细胞EGFR表达水平与长春瑞滨敏感度的相关性研究  

Correlation between EGFR Expression on Breast Cancer and NVB Sensitivity

作　　者：宁永玲[1,2] 谢叶文 陈洁[2] 周洪[1] 戚春建[2] 

机构地区：[1]南京医科大学基础医学院,南京210029 [2]南京医科大学附属常州市第二人民医院,常州213003

出　　处：《中国细胞生物学学报》2014年第3期343-348,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81272323);江苏省自然科学基金(批准号:BK2011244;BK2012590)资助的课题~~

摘　　要：乳腺癌是较早开始个体化治疗的肿瘤之一。表皮细胞生长因子受体(epidermal growth factor receptor,EGFR)的表达与乳腺癌组织学分期、生长速度呈正相关,可作为乳腺癌患者预后的指标之一。临床上,长春瑞滨(Vinorelbine,NVB)主要作为耐药性晚期乳腺癌的挽救性化疗药物,单药治疗亦具有一定疗效。该研究结果发现,乳腺癌组织EGFR表达与NVB的敏感性相关(P=0.001),而与紫杉醇、阿霉素及5-氟尿嘧啶无相关性。EGFR阴性乳腺癌细胞MDA-MB-435s对NVB耐药,而EGFR阳性细胞MCF-7则敏感,但是EGFR中和性抗体会降低敏感性。进一步研究发现,NVB会引起MCF-7表面EGFR表达上调,以及胞内ERK1/2激酶的磷酸化,且这一效应会被抗EGFR抗体部分抑制。研究结果表明,乳腺癌细胞对NVB的敏感性与膜表面EGFR表达水平相关,提示EGFR可作为NVB治疗敏感性的预测分子。Breast cancer treatment has been individualized for a long time. Epidermal growth factor receptor （EGFR）, whose expression level in tissue was generally associated with high tumor grade and elevated growth fraction, was a postoperative prognostic factor for breast cancer. As a salvage treatment after antbracyclines and taxanes in advanced breast cancer, vinorelbine （NVB） also had encouraging activity when used as a single agent. We found that EGFR expression in primary breast cancer specimens was significantly correlated with NVB sensitivity （P=0.001）, while no significant correlation with pachitaxel, adriamycin or 5-fluorouracil. EFGR- negative breast cancer line MDA-MB-435s was resistant to NVB, while EGFR-positive line MCF-7 had a high sensitivity to NVB which could be reduced by anti-EGFR antagonistic antibody. Moreover, NVB upregulated EGFR expression in MCF-7 and affected ERK1/2 phosphorylation consequently, which could be partially inhibited by pretreatment inhibitory anti-EGFR antibody. Our study showed that breast cancer cells sensitivity to NVB wasassociated with EGFR expression on cell membrane, suggesting EGFR expression may be used as a predictive marker for breast cancer treatment strategy.

关 键 词：长春瑞滨 表皮细胞生长因子受体 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]