DLIA／Notch信号通路对乳腺癌化疗药物转运及化疗耐药性影响的实验研究  

Experimental study of DLIA/Notch pathway function on chemoresistance and drug transporters in breast cancer

作　　者：王波[1] 张彤[2] 王群[3] 

机构地区：[1]湖北医药学院附属东风总医院器官移植乳腺外科,湖北省十堰市442008 [2]湖北医药学院附属东风总医院皮肤科,湖北省十堰市442008 [3]湖北医药学院外科教研室

出　　处：《中国医药》2015年第3期389-391,共3页China Medicine

基　　金：湖北省教育厅科研项目（Q20132107）

摘　　要：目的探讨DLL4／Notch信号通路对乳腺癌药物转运及其对化疗耐药性影响。方法将24只雌性重症联合免疫缺陷小鼠完全随机分为观察组与对照组，每组12只，分别将BaF3-DLL4与BaF3．CK稳定转染乳腺癌细胞注射入观察组与对照组小鼠腋下成瘤，进行肿瘤血管体积系数与荧光灌注试验；选择形成肿瘤的裸鼠腹腔注射吉西他滨100mg／kg，比较2组的肿瘤血管体积系数、化疗药物灌注荧光率、血液灌注荧光率和吉西他滨治疗后2，3，4，5周肿瘤体积。结果观察组肿瘤血管体积系数（0．014±0．001）明显低于对照组（0．006±0．001），差异有统计学意义（P〈0．05）。观察组化疗药物灌注荧光率及血液灌注荧光率均明显低于对照组[（0．76±0．49）％比（1．34±0．45）％，（0．38±0．11）％比（0．64±0．22）％，均P〈0．05）。吉西他滨化疗治疗4、5周后对照组肿瘤体积大于观察组，对照组分别为（120±24）、（159±44）mm^3，观察组分别为（91±15）、（93±15）mm^3，差异有统计学意义（P〈0．05）。结论DLIA／Notch信号通路过度激活可引起乳腺癌血液灌注障碍，从而影响乳腺癌化疗药物转运，增强乳腺癌化疗耐药性。Objective To investigate the chemoresistance and drug transporters of DLL4/Notch pathway in breast cancer. Methods Totally 24 female mice with severe combined immunodeficiency flat were equally divided into the observation group （ n = 6 ） and the control group （ n = 6 ）. The BaF3-DLL4 and BaF3-CK cells were injected into the mice for tumor formation; the tumor vascular volume coefficient and fluorescent perfusion were tested; the formation tumors mice had gemcitabine. The tumor vascular volume coefficient, fluorescent chemotherapy infusion rate, blood perfusion fluorescence ratio and tumor volume between two groups were analyzed. Results The tumor vascular volume coefficient of the observation group was（0. 014 ±0. 001 ） , significantly lower than that in the control group （0. 006 ±0. 001 ） , （ P 〈 0.05 ）. The chemotherapy infusion fluorescence rates and blood perfusion fluorescence rates in the observation group were significantly lower than those in control group [ （ 0.76 ± 0.49 ） % and （ 0.38± 0.11）% vs （1.34±0.45）% and （0.64 ±0.22）% , P〈0.05）. After emcitabine chemotherapy for 4-5 weeks, the tumor volume in the control group and observation group was （120 ± 24）, （159 ± 44） mm^3 vs （91± 15） , （93 ± 15） mm^3（p 〈0.05）. Conclusions DLL4/Notch pathway excessive activation can induce blood perfusion disorder; it can affect chemotherapy drug transporters in the breast cancer to increase breast cancer chemotherapy drug resistance.

关 键 词：DLL4/Notch信号通路 乳腺癌 化疗耐药性 药物转运 

分 类 号：R737.9[医药卫生—肿瘤]