曲妥珠和曲妥珠单抗美坦新衍生物对不同乳腺癌细胞系的生物学效应研究

王兰,于传飞,杨雅岚,武刚,郭莎,刘春雨,张峰,王文波,李萌,陈伟,高凯

中国药学杂志 ›› 2016, Vol. 51 ›› Issue (13) : 1096-1100.

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中国药学杂志 ›› 2016, Vol. 51 ›› Issue (13) : 1096-1100. DOI: 10.11669/cpj.2016.13.009
重组药物及单克隆药物质量检测研究专栏

曲妥珠和曲妥珠单抗美坦新衍生物对不同乳腺癌细胞系的生物学效应研究

  • 王兰,于传飞,杨雅岚,武刚,郭莎,刘春雨,张峰,王文波,李萌,陈伟,高凯
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Biological Effects of Trastuzumab and T-DM1 on Different Breast Cancer Lines

  • WANG Lan, YU Chuan-fei, YANG Ya-lan, WU Gang, GUO Sha, LIU Chun-yu, ZHANG Feng, WANG Wen-bo, LI Meng, CHEN Wei, GAO Kai
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摘要

目的 研究曲妥珠和曲妥珠单抗美坦新衍生物(T-DM1)对BT-474和HCC1954两种乳腺癌细胞系的不同生物学效应。方法 运用流式细胞术检测两种细胞系中人表皮生长因子受体2(HER2)表达水平;运用酶联免疫吸附测定法(ELISA)检测曲妥珠和曲妥珠单抗美坦新衍生物与人表皮生长因子受体2抗原的结合能力;运用细胞增殖抑制/杀伤法,检测曲妥珠和曲妥珠单抗美坦新衍生物对两种细胞系的剂量反应曲线。结果 人表皮生长因子受体2在两种细胞系中表达水平均较高;曲妥珠和曲妥珠单抗美坦新衍生物与人表皮生长因子受体2抗原的结合能力相似;曲妥珠对BT474具有增殖抑制作用,但是对HCC1954无作用,曲妥珠单抗美坦新衍生物则对BT474和HCC1953均具有杀伤作用。结论 在细胞学模型中,曲妥珠单抗美坦新衍生物可以对人表皮生长因子受体2高表达但是曲妥珠耐药的细胞系具有生物学效应。

Abstract

OBJECTIVE To investigate the different biological effects of trastuzumab and T-DM1 on BT-474 and HCC1954 cell lines.METHODS Flow cytometry was employed to study the expression level of HER2 on the two cell lines. ELISA was used to check the binding ability of trastuzumab and T-DM1 with HER2 antigen. With cell proliferation inhibition and killing methods, the dose-response curves were explored to demonstrate the biological effects of trastuzumab and T-DM1 on the two cell lines. RESULTS HER2 were highly expressed in both of the two cell lines. The HER2 binding ability was highly similar between trastuzumab and T-DM1. Trastuzumab could inhibit the proliferation of BT474 but not HCC1954, while T-DM1 could kill both kinds of cells. CONCLUSION In the in vitro cell models, T-DM1 can play biological effect in HER2 highly expressed but trastuzumab-resistant cell lines.

关键词

曲妥珠 / 曲妥珠单抗美坦新衍生物 / BT474 / HCC1954 / 耐药

Key words

trastuzumab / T-DM1 / BT474 / HCC1954 / drug-resistant

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王兰,于传飞,杨雅岚,武刚,郭莎,刘春雨,张峰,王文波,李萌,陈伟,高凯. 曲妥珠和曲妥珠单抗美坦新衍生物对不同乳腺癌细胞系的生物学效应研究[J]. 中国药学杂志, 2016, 51(13): 1096-1100 https://doi.org/10.11669/cpj.2016.13.009
WANG Lan, YU Chuan-fei, YANG Ya-lan, WU Gang, GUO Sha, LIU Chun-yu, ZHANG Feng, WANG Wen-bo, LI Meng, CHEN Wei, GAO Kai. Biological Effects of Trastuzumab and T-DM1 on Different Breast Cancer Lines[J]. Chinese Pharmaceutical Journal, 2016, 51(13): 1096-1100 https://doi.org/10.11669/cpj.2016.13.009
中图分类号: R963   

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基金

国家科技重大专项重大新药创制资助项目(2014ZX09304311-001);中国食品药品检定研究院学科带头人培养基金资助项目(2013X3)
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