头颈鳞癌Notch1的表达与顺铂敏感性的关系  

Correlation of Notch1 expression and activation to cisplatin-sensitivity of head and neck squamous cell carcinoma

作　　者：张祖平[1] 孙玉兰[2] 付丽[2] 谷峰[2] 张仑[1] 郝希山[3] 

机构地区：[1]天津医科大学附属肿瘤医院头颈一科,天津300060 [2]乳腺癌防治教育部重点实验室,天津医科大学附属肿瘤医院乳腺病理研究室,天津300060 [3]天津医科大学附属肿瘤医院,天津300060

出　　处：《癌症》2009年第2期122-125,共4页Chinese Journal of Cancer

基　　金：教育部留学回国人员科研启动基金(No.2008101)~~

摘　　要：背景与目的:Notch1属于Notch跨膜受体家族,在肿瘤细胞增殖和凋亡过程中发挥着重要作用。已有研究表明Notch1影响化疗药物敏感性。而Notch1与头颈鳞癌顺铂敏感性的关系仍未被阐明。本研究旨在明确Notch1在头颈鳞癌中的表达状况,探讨Notch1表达水平对头颈鳞癌顺铂敏感性的影响。方法:收集25例头颈鳞癌新鲜手术标本进行原代细胞培养,肿瘤原代细胞胶原凝胶体包埋化疗药物敏感性检测(collagen gel droplet embedded culture-drug sensitivity test,CD-DST)技术检测顺铂敏感性。免疫化学染色检测头颈鳞癌、正常鳞状上皮和舌鳞癌细胞株(Tb3.1)Notch1的表达水平。将经二甲基亚砜(dimethyl sulfoxide,DMSO)、DAPT处理后的Tb3.1细胞分4组(DMSO、DAPT、DMSO+Cisplatin、DAPT+Cisplatin),顺铂作用后CD-DST检测各组吸光度值。结果:头颈鳞癌组织Notch1阳性表达,表达水平明显高于正常鳞状上皮(P<0.001),且与顺铂敏感性呈负相关(r=-0.705,P<0.01)。Tb3.1细胞Notch1阳性表达,DMSO组(A值155.4±2.3)与DAPT组(A值154.7±1.2)吸光度值差异无统计学意义(P>0.05),而DMSO+Cisplatin组(A值33.9±1.3)与DAPT+Cisplatin组(A值26.6±1.1)吸光度值差异具有统计学意义(P<0.05)。结论:Notch1在头颈鳞癌中表达,且表达水平与顺铂的敏感性呈负相关。Notch1可用于预测头颈鳞癌顺铂的敏感性;DAPT阻断Notch1信号通路可提高Tb3.1细胞顺铂的敏感性。Background and Objective. Notch1 beJongs to the Notch famiJy of transmembrane receptors and plays an important role in tumor cell proliferation and apoptosis. Notch1 affects chemosensitivity of tumors. However, its correlation to cisplatin （DDP）-sensitivity of head and neck squamous cell carcinoma is unclear. This study was to identify the expression of Notch1 in head and neck squamous celt carcinoma, and investigate its influence on the DDP-sensitivity. Methods： Twenty-five fresh specimens of head and neck squamous cell carcinoma were subjected to primary cell culture. DDP- sensitivity of tumor cells was detected using collagen gel droplet embedded culture-drug sensitivity test （CD-DST）. The expression of Notch1 in head and neck squamous cell carcinoma, normal squamous epithelium, and tongue squamous cell carcinoma Tb3.1 cells was detected by immunohistochemistry or immuocytochemistry. Tb3.1 cells were divided into four groups, and received treatment of DMSO, DAPT, DMSQ plus DDP, DAPT plus DDP, respectively. The absorbance of the four groups was detected by CD-DST to evaluate DDP-sensitivity. Results. The positive rate of Notch1 was significantly higher in head and neck squamous cell carcinoma than in normal squamous epithelium （100% vs. 35%, P〈0.001）, and it was negatively correlated to DDP-sensitivity （r=-0.705, P〈0.01）. There was no difference in absorbance between DMSO group and DAPT group （155.4＋2.3 vs. 154.7±1.2, P〉0.05）, while the absorbance was significantly higher in DMSO plus DDP group than in DAPT plus DDP （33.9±1.3 vs. 26.6±1.1, P〈0.05）. Conclusions. Notch1 expression is negatively correlated to DDP-sensitivity of head and neck squamous cell carcinoma, and could be used to predict DDP- sensitivity. DAPT can enhance DDP-sensitivity of Tb3.1 cells via blocking Notch1 signaling.

关 键 词：头颈肿瘤 鳞状细胞癌 顺铂 药物敏感性 NOTCH1 

分 类 号：R739.91[医药卫生—肿瘤]