2018 年第 10 期 第 13 卷

表皮生长因子联合阿霉素对乳腺癌裸鼠移植瘤的作用及残存肿瘤细胞特性

Effect of epidermal growth factor combined with doxorubicin on xenograft breast cancer in nude mice and the characteristics of residual tumour cells

作者：蔡威滕莉黄开禹王向阳王辉

英文作者：

单位：430014武汉市中医医院外科（蔡威）；430014华中科技大学同济医学院附属武汉中心医院胃肠外科分子诊断湖北省重点实验室（滕莉、黄开禹、王向阳、王辉）

英文单位：

关键词：乳腺肿瘤；表皮生长因子；阿霉素；新型肿瘤细胞

英文关键词：

• 摘要：

• 【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-MB-415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-MB-415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）mm3比（757±28）mm3、（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）mm3比（1 601±76）mm3、（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。

• 【Abstract】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）mm3 vs （757±28）mm3, （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）mm3 vs （1 601±76）mm3, （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.