解剖学报

解剖学报 ›› 2020, Vol. 51 ›› Issue (4): 536-542.doi: 10.16098/j.issn.0529-1356.2020.04.010

• 肿瘤生物学 • 上一篇    下一篇

载和厚朴酚玉米蛋白纳米递药系统的制备及体外的抗乳腺癌活性

刘丹 王婧* 王良 彭瑶   

  1. 齐齐哈尔医学院医药科学研究院，黑龙江 齐齐哈尔 161000
  • 收稿日期:2019-06-05 修回日期:2020-03-05 出版日期:2020-08-06 发布日期:2020-08-06
  • 通讯作者: 王婧 E-mail:wangjing@qmu.edu.cn
  • 基金资助:
    黑龙江省教育厅科学技术研究项目

Preparation of honokiol-loaded zein nano-drug delivery system and its anti-breast cancer activity in vitro#br#

LIU Dan WANG Jing* WANG Liang PENG Yao   

  1. Institute of Medical Sciences, Qiqihar Medical University, Heilongjiang Qiqihar 161000, China
  • Received:2019-06-05 Revised:2020-03-05 Online:2020-08-06 Published:2020-08-06
  • Contact: WANG Jing E-mail:wangjing@qmu.edu.cn

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摘要：

目的 制备低生物毒性载和厚朴酚（HNK）的玉米蛋白（zein）纳米递药系统（Zein-HNK），探讨该系统对乳腺癌细胞系MDA-MB-231的抑制作用。 方法 抗溶剂法制备Zein-HNK纳米递药系统。考察其粒径、分散度、形貌特征、包封率及体外释放行为。评价该系统对MDA-MB-231细胞增殖、凋亡、迁移和侵袭能力的影响。  结果 Zein-HNK纳米递药系统粒径为（83.75±2.95）nm；聚合物分散性指数（PDI）为0.132±0.015；对HNK的包封率为（93.04±1.86）%。体外释放实验24 h释放率： Zein-HNK组为（69.10±1.88）%；阳性对照游离-HNK（Free-HNK）组为（88.90%±2.58）%。细胞毒评价：MDA-MB-231细胞阳性对照Free-HNK组MDA-MB-231细胞IC50为（5.02±0.29）mg/L，MCF-7细胞半抑制浓度（IC50）为（4.72±0.22）mg/L；Zein-HNK组MDA-MB-231细胞IC50为（9.92±1.02）mg/L，MCF-7细胞IC50为（9.35±0.30）mg/L。凋亡率：阴性对照control组（8.73±0.64）%；Zein-HNK组（15.05±0.85）%；阳性对照Free-HNK组（28.54±1.48）%（P<0.05）；迁移指数：control组0.67±0.04；ZeinHNK组0.55±0.03；Free-HNK组0.36±0.03（P<0.05）；侵袭相对数：control组0.66±0.03，Zein-HNK组0.44±0.01和Free-HNK组0.35±0.03（P<0.01）。Western blotting结果显示，Zein-HNK通过降低Bcl-2的表达和增加Bax的表达来诱导细胞凋亡。 结论 Zein-HNK纳米递药系统可有效降低HNK的毒副作用，通过抑制乳腺癌细胞增殖，诱导细胞凋亡，同时抑制细胞迁移和侵袭，达到抑制乳腺癌细胞MDA-MB-231活性的目的。

关键词: 和厚朴酚, 玉米蛋白, 纳米递送系统, 乳腺癌细胞系, 免疫印迹法

Abstract:

Objective To prepare a honokiol (HNK)-loaded zein nano-drug delivery system with low biotoxicity and to investigate its inhibitory effect on MDA-MB-231 breast cancer cells.  Methods Zein-HNK nano-drug delivery system was prepared by anti-solvent method . The particle size, dispersion, morphological characteristics, encapsulation efficiency and in vitro release behavior of the system were investigated. The effects of this system on the proliferation, apoptosis, migration and invasion of MDA-MB-231 cells were evaluated.   Results The particle size of Zein-HNK was (83.75±2.95) nm and the polymer dispersity index(PDI) of it was 0.132±0.015. The encapsulation efficiency of HNK was (93.04±1.86)%. The in vitro release rate of Free-HNK group was(88.90%±2.58)% and release rate of Zein-HNK group was (69.10±1.88）% at 24 hours. Cytotoxicity evaluation showed the 50% inhibiting concentration(IC50) of MDA-MB-231 cells in the positive control group was (5.02±0.29) mg/L, which of MCF-7 cells was (4.72±0.22) mg/L; and the IC50 of MDA-MB-231 cells in Zein-HNK group was (9.92±1.02) mg/L, which of MCF-7 was (9.35±0.30) mg/L. The apoptotic rates of control group, Zein-HNK group and Free-HNK group were (8.73±0.64)%, (15.05±0.85)% and (28.54±1.48)%, respectively. Migration index was 0.67±0.04 in the control group, 0.55±0.03 in the Zein-HNK group and 0.36±0.03 in the Free-HNK group (P<0.05). The relative number of invasions was 0.66±0.03 in the control group, 0.44±0.01 in the Zein-HNK group and 0.35±0.03 in the Free-HNK group (P<0.01). Western bltting result showed that Zein-HNK induced cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax.   Conclusion Zein-HNK nano-drug delivery system can effectively reduce the toxic and side effects of HNK itself. Zein-HNK nano-drug delivery system can effectively inhibit breast cancer proliferation, induce cell apoptosis, and inhibit cell migration and invasion simultaneously.

Key words: Honokiol, Zein, Nano-delivery system, Breast cancer cell line, Western blotting
 

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