国际肿瘤学杂志

国际肿瘤学杂志 ›› 2016, Vol. 43 ›› Issue (8): 641-645.doi: 10.3760/cma.j.issn.1673422X.2016.09.001

• 论著 • 上一篇    下一篇

转铁蛋白修饰多柔比星脂质体靶向抑制乳腺癌细胞增殖的研究

樊华,刘敏丽,常琦,刘勇峰,孙学军,张生军   

  1. 716000 延安大学附属医院普外科（樊华、常琦、刘勇峰、张生军），病理教研室（刘敏丽）；西安交通大学附属第一医院普外科（孙学军）
  • 出版日期:2016-09-08 发布日期:2016-08-04
  • 通讯作者: 张生军，Email： zhangshengjun1973@126.com E-mail:zhangshengjun1973@126.com
  • 基金资助:

    国家自然科学基金（81172362）；陕西省科技统筹创新工程计划（2013KTCQ0308）

Study of transferrin modified doxorubicin liposome targeted to inhibit proliferation of breast cancer cells

Fan Hua, Liu Minli, Chang Qi, Liu Yongfeng, Sun Xuejun, Zhang Shengjun   

  1. Department of General Surgery, Affliated Hospital of Yan′ an University, Yan′ an 716000, China
  • Online:2016-09-08 Published:2016-08-04
  • Contact: Zhang Shengjun E-mail:zhangshengjun1973@126.com
  • Supported by:

    National Natural Science Foundation of China (81172362); Science and Technology Innovation Project Plan of Shaanxi Porvince of China (2013KTCQ0308)

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摘要： 【摘要】目的利用转铁蛋白（TF）修饰多柔比星脂质体，并探讨其对乳腺癌细胞增殖的影响。方法采用薄膜超声法制备脂质体，利用硫酸梯度法制备多柔比星脂质体，然后采用后插入法制备TF修饰多柔比星脂质体。激光共聚焦显微镜检测乳腺癌细胞MCF7和MDAMB231对TF多柔比星脂质体的摄取，四甲基偶氮唑盐比色法(MTT法)检测TF多柔比星脂质体靶向作用MCF7和MDAMB231细胞后的杀伤能力，软琼脂克隆集落实验检测TF多柔比星脂质体对MCF7和MDAMB231细胞的生长抑制作用。结果激光共聚焦显微镜观察显示，MCF7细胞和MDAMB231细胞对TF多柔比星脂质体摄取率显著高于多柔比星脂质体；MTT法检测结果则显示，TF多柔比星脂质体对MCF7细胞［（20.8±3.2）μmol/L］和MDAMB231细胞［（20.1±3.0）μmol/L］杀伤的IC50显著低于多柔比星脂质体［（158.6±24.6）μmol/L；（160.1±25.1）μmol/L）］和游离多柔比星［（161.7±26.2）μmol/L；（166.9±27.0）μmol/L）］，差异有统计学意义（F=116.03，P<0.001；F=75.29，P<0.001）。软琼脂克隆集落实验显示，TF多柔比星脂质体对克隆集落的生长抑制显著优于多柔比星脂质体、游离多柔比星及对照组［MDAMB231细胞直径:（60.5±10.4）μm、（94.3±16.8）μm、（131.8±22.6）μm、（162.8±30.3）μm；MCF7细胞直径:（31.8±5.5）μm、（62.1±11.1）μm、（108.6±18.6）μm、（157.4±29.3）μm］，差异有统计学意义（F=87.17，P＜0.000 1；F=178.23，P＜0.000 1）。结论TF多柔比星脂质体对乳腺癌细胞体外增殖具有显著的抑制作用，能够高效、特异地杀死乳腺癌细胞，为体内治疗乳腺癌提供了一定的理论依据。

关键词: 转铁蛋白, 多柔比星, 脂质体, 乳腺肿瘤

Abstract: 【Abstract】ObjectiveTo modified doxorubicin liposome with transferrin（TF）, and to investigate its inhibition efficacy on the proliferation of human breast cancer cells. MethodsThe liposome was prepared by thin film ultrasonic, and doxorubicin liposomal was prepared by sulfuric acid gradient. The TFdoxorubicin liposome was prepared by the post insertion method. The uptake of TFliposomal doxorubicin on breast cancer cells MCF7 and MDAMB231 were detected by confocal microscopy. The killing ability of TFdoxorubicin liposomal targeting for MCF7 and MDAMB231 were detected by MTT assay. Inhibitory effect of TFdoxorubicin liposome on the growth of MCF7 and MDAMB231 were detected by soft agar colony assay. ResultsConfocal microscopy result showed that the uptake of TFliposomal doxorubicin on MCF7 and MDAMB231 were significantly higher than doxorubicin liposomal. Cellkilling ability on MCF7 and MDAMB231 showed that the IC50 in TFliposomal doxorubicin ［MCF7 cells:（20.8±3.2）μmol/L; MDAMB231 cells:（20.1±3.0）μmol/L）］ were significantly lower than the liposomal ［（158.6±24.6）μmol/L; （160.1±25.1）μmol/L）］ and free doxorubicin ［（161.7±26.2）μmol/L;（166.9±27.0）μmol/L）］, with significant differences（F=116.03，P<0.001; F=75.29， P<0.001）. Soft agar colony assay showed that the inhibition of TFdoxorubicin liposome on colony growth were significantly higher than doxorubicin liposome, free doxorubicin and control ［diameter of MDAMB231 cells:（60.5±10.4）μm, （94.3±16.8）μm, （131.8±22.6）μm, （162.8±30.3）μm; diameter of MCF7 cells:（31.8±5.5）μm, （62.1±11.1）μm, （108.6±18.6）μm, 157.4±29.3）μm］ , with significant differences (F=87.17， P＜0.000 1；  F=178.23， P＜0.000 1). ConclusionTFdoxorubicin liposome has a significant inhibitory effect on the proliferation of breast cancer cells in vitro, and can effectively and specifically kill the breast cancer cells, which provides theoretical basis for the treatment of breast cancer in vivo.

Key words: Transferrin, Doxorubicin, Liposomes, Breast neoplasms