摘要
目的探讨表皮生长因子(EGF)联合阿霉素对乳腺癌裸鼠移植瘤的作用,并初步分析其机制及残存细胞的特性。方法建立裸鼠(Balb/c-nu)乳腺癌MDA-MB415细胞的移植瘤模型,观察EGF联合阿霉素(EGF+阿霉素组)及单纯阿霉素化疗(阿霉素组)对MDA-MB415细胞的成瘤能力及抑瘤率,并检测Ki-67及细胞周期蛋白A、B、D、E的表达、肿瘤干细胞标志物CD_(44)^+/CD_(24)^-阳性细胞比例,以及残存肿瘤细胞的成瘤能力。结果 EGF+阿霉素组肿瘤体积和质量均小于阿霉素组[(354±21)mm^3比(757±28) mm^3、(226±19) mg比(525±18) mg],抑瘤率高于阿霉素组(73. 9%比39.4%),差异均有统计学意义(均P<0.05)。EGF+阿霉素组Ki-67表达高于阿霉素组[(51±8)%比(35±6)%],细胞周期蛋白A、B、D、E表达均低于阿霉素组[(32±5)比(51±6)、(30±6)比(48±7)、(31±10)比(53±9)、(42±7)比(65±10)], CD_(44)^+/CD_(24)^-阳性率高于阿霉素组[(8. 0±0. 6)%比(4. 6±0.5)%],差异均有统计学意义(均P <0.05)。EGF+阿霉素组二次成瘤肿瘤体积和质量均明显大于阿霉素组[(2 176±97)mm^3比(1 601±76)mm^3、(1 752±88)mg比(1 246±19)mg],差异均有统计学意义(均P<0.05)。结论 EGF可增强乳腺癌细胞对阿霉素的敏感度,其机制可能与EGF诱导处于静止期肿瘤细胞增殖有关,EGF与阿霉素联合处理组肿瘤残留细胞可能为一群低表达细胞周期蛋白的肿瘤细胞亚群,该亚群细胞成瘤能力更强。
Objective To explore the effect of epidermal growth factor（EGF） combined with doxorubicin（DXR） on xenograft breast cancer in nude mice and to analyze the characters of residual tumor cells. Methods Breast cancer xenograft model was established using MDA-MB-415 cell line and Balb/c-nu mice. After tumor formation, the mice were treated with EGF plus DXR and DXR alone. Volume and mass of xenograft tumor, tumor inhibition rate, Ki-67, cyclin A, B, D, E expression, tumor stem cell marker CD＋44/CD-24 positive rate and the tumorigenic ability of residual tumor cells were analyzed. Results Volume and mass of xenograft tumor in the EGF＋DXR group were less than those in the DXR-alone group[（354±21）mm^3 vs （757±28）mm^3, （226±19）mg vs （525±18）mg]; the tumor inhibition rate in the EGF＋DXR group was higher than that in the DXR-alone group（73.9% vs 39.4%）（all P〈0.05）. Ki67 expression in the EGF＋DXR group was higher than that in the DXR group[（51±8）% vs （35±6）%]; expressions of cyclin A, B, D, E in the EGF＋DXR group were lower than those in the DXR group[（32±5） vs （51±6）, （30±6） vs （48±7）, （31±10） vs （53±9）, （42±7） vs （65±10）]; CD＋44/CD-24 positive rate in the in the EGF＋DXR group was higher than that in the DXR group[（8.0±0.6）% vs （4.6±0.5）%]（all P〈0.05）. Volume and mass of the xenograft tumor induced by residual tumor cells in the EGF＋DXR group were greater than those in the DXR-alone group[（2 176±97）mm^3 vs （1 601±76）mm^3, （1 752±88）mg vs （1 246±19）mg]（all P〈0.05）. Conclusions EGF can enhance the sensitivity of breast cancer cells to DXR; the possible mechanism is that EGF induces cancer cells in stationary phase into proliferative phase. Residual cancer cells treated by EGF plus DXR may be a new type of subgroup with low cyclins and strong tumorigenic ability.
作者
蔡威
滕莉
黄开禹
王向阳
王辉
Cai Wei;Teng Li;Huang Kaiyu;Wang Xiangyang;Wang Hui(Department of Surgery,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430014,China（Cai W;Department of Gastrointestinal Surgery,the Central Hospital of Wuhan,Tongji Medical College of Huazhong University of Science and Technology,Key Laboratory for Molecular Diagnosis of Hubei Province,Wuhan 430014,China（Teng L.Huang KY.Wanz XY.Wang)
出处
《中国医药》
2018年第10期1555-1558,共4页
China Medicine
基金
湖北省自然科学基金(2015CFB542)
湖北省卫生和计划生育委员会资助项目(WJ2015Z067)
武汉市卫生和计划生育委员会资助项目(WX15D62)~~
关键词
乳腺肿瘤
表皮生长因子
阿霉素
新型肿瘤细胞
Breast neoplasms
Epidermal growth factor
Doxorubicin
New tumor cells
