南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (06): 876-883.doi: 10.12122/j.issn.1673-4254.2020.06.16

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攀登鱼藤异黄酮脂质体有较好的物理性能及抗乳腺癌细胞的增殖活性

毛联智，刘会平，刘华缓，卞中博，张秋玉，廖文镇，孙素霞   

  • 出版日期:2020-06-20 发布日期:2020-06-20
  • 基金资助:

Preparation of warangalone-loaded liposomes and its inhibitory effect on breast cancer cells

  

  • Online:2020-06-20 Published:2020-06-20

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摘要： 目的 制备和鉴定攀登鱼藤异黄酮温敏脂质体并研究其抗乳腺癌作用。方法 MTT法检测攀登鱼藤异黄酮、大豆异黄酮和金雀异黄酮对人乳腺癌细胞（MDA-MB-231、MCF7、SKBR3）增殖活性影响；克隆形成实验探讨攀登鱼藤异黄酮对三阴性乳腺癌细胞（MDA-MB-231）克隆形成的影响；细胞划痕实验检测MDA-MB-231细胞迁移；蛋白印迹法检测MDA-MB-231细胞迁移和侵袭蛋白MMP2，MMP9表达量；薄膜水化法制备温敏脂质体及攀登鱼藤异黄酮温敏脂质体；透射电子显微镜、动态光散射扫描仪以及紫外分光光度计分别鉴定攀登鱼藤异黄酮温敏脂质体形貌、粒径、包封率及稳定性，并用MTT法检测攀登鱼藤异黄酮温敏脂质体抗小鼠乳腺癌细胞（4T1）增殖活性。结果 攀登鱼藤异黄酮可显著抑制人乳腺癌细胞（MDA-MB-231、MCF7、SKBR3）增殖，且效果优于大豆异黄酮和金雀异黄酮；攀登鱼藤异黄酮显著减少三阴性乳腺癌细胞（MDA-MB-231）克隆形成量，降低其划痕面积的愈合速度，并下调MMP2和MMP9的表达。薄膜水化法制备得到的温敏脂质体呈均质不规则球形，其粒径为56.23±0.61 nm、聚合物分散指数为0.241±0.014、Zeta电位为-40.40±0.46 mV、包封率为（87.68±2.41）%、稳定性较好，且抗小鼠乳腺癌增殖活性增强。结论 攀登鱼藤异黄酮通过抑制乳腺癌细胞增殖、转移和侵袭发挥其抗癌活性，攀登鱼藤异黄酮温敏脂质体具有较好的物理性能及抗乳腺癌活性。

Abstract: Objective To prepare warangalone-loaded thermosensitive liposomes (WLTSL) and evaluate its inhibitory effect on breast cancer cells in vitro. Methods MTT assay was used to assess the changes in proliferation of 3 breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) following treatment with warangalone, soy isoflavone and genistein. Colony-forming assay and wound healing assay was used to assess colony forming activity and migration of MDA-MB-231 cells treated with warangalone. The effect of warangalone on the expression of MMP2 and MMP9 in MDA-MB-231 cells was examined with Western blotting. The thermosensitive liposomes (TSL) and WLTSL were prepared using a thin film hydration method, and the morphology, size, encapsulation efficiency and stability of the prepared liposomes were characterized using transmission electron microscopy, dynamic light scattering scanning and UV spectrophotometry. MTT assay was used to examine the inhibitory effect of WLTSL on mouse breast cancer cells (4T1) in vitro. Results Warangalone showed stronger anti-proliferation effects than soy isoflavones and genistein in the 3 human breast cancer cell lines and significantly inhibited colony formation by MDA-MB-231 cells. Treatment with warangalone significantly inhibited migration of the breast cancer cells and downregulated the cellular expressions of MMP2 and MMP9. The prepared TSL and WLTSL presented with a homogeneous, irregular spherical morphology, with a mean particle size of 56.23±0.61 nm, a polymer dispersity index of 0.241±0.014, a Zeta potential of -40.40±0.46 mV, and an encapsulation efficiency was 87.68±2.41%. WLTSL showed a good stability at 4 ℃ and 37 ℃ and a stronger inhibitory effect than warangalone in 4T1 cells. Conclusion Warangalone inhibits the proliferation, migration and invasion of breast cancer cells, and the prepared WLTSL possesses good physical properties and strong anti-breast cancer activity.