2018 年第 5 期 第 13 卷

联合应用盐酸小檗碱和紫杉醇对乳腺癌MCF-7细胞生长及上皮-间质细胞转化的影响

Effect of berberine hydrochloride combined with paclitaxel on cell growth and epithelial-mesenchymal transition of human breast cancer cell line MCF-7

作者：?程实庞博安成孙士鹏侯雪筠叶红蕾刘贵建康熙雄

英文作者：

单位：100050首都医科大学附属北京天坛医院检验科［程实（现工作单位为中国中医科学院广安门医院检验科）、康熙雄］；100053北京，中国中医科学院广安门医院检验科（庞博、安成、孙士鹏、侯雪筠、叶红蕾、刘贵建）

英文单位：

关键词：乳腺癌MCF-7细胞；盐酸小檗碱；紫杉醇

英文关键词：

• 摘要：

• 目的    探讨盐酸小檗碱（BBR）和紫杉醇联合应用对雌激素受体阳性乳腺癌细胞MCF-7生长及上皮-间质细胞转化的影响。方法    体外培养雌激素受体阳性乳腺癌MCF-7细胞，随机分为对照组、紫杉醇组、BBR组以及联合用药组。显微镜下观察细胞数量、形态的变化；应用细胞增殖检测试剂盒检测细胞增殖情况；流式细胞仪分析细胞周期分布及凋亡的变化；实时荧光定量聚合酶链反应检测上皮钙黏蛋白（E-cad）和神经钙黏蛋白（N-cad）基因的表达。结果    联合用药组（紫杉醇+BBR 5.0、50 μmol/L组）用药72 h后细胞增殖率明显低于对照组［（21.2±8.0）%、（22.2±2.8）%比（83.9±0.0）%］（均P＜0.05）。联合用药组（紫杉醇+BBR 50 μmol/L）显微镜下可见细胞凋亡的明显特征。联合用药组（紫杉醇+BBR 12.5、25、50、100 μmol/L组）MCF-7细胞早期凋亡比例均明显高于对照组［（28.2±0.8）%、（24.4±4.1）%、（30.0±1.7）%、（29.6±5.2）%比（7.2±0.7）%］和紫杉醇组［(9.8±2.2)%］，差异均有统计学意义（均P＜0.05）。联合用药组（紫杉醇+BBR 25、50 μmol/L组）G0/G1期细胞比例明显高于紫杉醇组和BBR 25、50 μmol/L组（均P＜0.05）。用药48 h后，紫杉醇组N-cad基因表达量明显高于对照组和紫杉醇+BBR 10 μmol/L组（均P＜0.05），紫杉醇+BBR 10 μmol/L组E-cad基因表达量与紫杉醇组、对照组比较，差异均无统计学意义（均P＞0.05）。结论    BBR和紫杉醇联合应用对乳腺癌MCF-7细胞具有协同抑制作用，能促进细胞凋亡，阻断细胞周期，并且抑制N-cad基因表达，降低乳腺癌细胞的侵袭转移能力，改善紫杉醇的治疗效果。

• 【Abstract】Objective    To explore the effect of berberine hydrochloride(BBR) combined with paclitaxel on cell growth and epithelial-mesenchymal transition of estrogen receptor positive breast cancer cell line MCF-7. Methods    Breast cancer cell line MCF-7 was cultured in vitro and randomized into control group, paclitaxel group, BBR group and combination group. Changes of cell number and morphology were observed under microscope; cell proliferation was detected by cell counting kit-8; cell cycle percentage and apoptosis were analyzed by flow cytometry; gene expressions of epithelial cadherin（E-cad） and nerve cadherin（N-cad） were detected by real-time fluorescence quantitative polymerase chain reaction. Results    Cell proliferation rate 72 h after drug intervention in combination group(paclitaxel+BBR 5.0, 50 μmol/L groups) was significantly lower than that in control group［（21.2±8.0）%,（22.2±2.8）% vs （83.9±0.0）%］（P＜0.05）. Signs of cell apoptosis could be observed under microscope in combination group(paclitaxel+BBR 50 μmol/L group). Cell early apoptosis ratio in combination group(paclitaxel+BBR 12.5, 25, 50, 100 μmol/L groups) was significantly higher than that in control group［（28.2±0.8）%,（24.4±4.1）%,（30.0±1.7）%,（29.6±5.2）% vs （7.2±0.7）%］ and paclitaxel group［(9.8±2.2)%］(P＜0.05). Cell G0/G1 phase ratio in combination group(paclitaxel+BBR 25, 50 μmol/L groups) was significantly higher than that in paclitaxel group and BBR 25, 50 μmol/L groups(P＜0.05). N-cad gene expression 48 h after drug intervention in paclitaxel group was significantly higher than that in control group and paclitaxel+BBR 10 μmol/L group（P＜0.05）; E-cad gene expression showed no significant difference among paclitaxel group, control group and paclitaxel+BBR 10 μmol/L group（P＞0.05）. Conclusions    Combined application of BBR and paclitaxel has a synergistic inhibitory effect on breast cancer MCF-7 cell proliferation; it can promote cell apoptosis, block cell cycle, inhibit N-cad gene expression and reduce cell invasion and metastasis. The therapeutic effect of paclitaxel can be improved in combination with berberine.

  【Key words】Breast cancer cell MCF-7；Berberine hydrochloride；Paclitaxel

  【Fund program】National Natural Science Foundation of China（81641192）