国际口腔医学杂志

国际口腔医学杂志 ›› 2025, Vol. 52 ›› Issue (2): 195-204.doi: 10.7518/gjkq.2025008

• 论著 • 上一篇    下一篇

转铁蛋白修饰的姜黄素脂质体对口腔鳞状细胞癌细胞株HN4增殖抑制机制的研究

魏雪琴(),巴凯   

  1. 郑州大学第一附属医院口腔医学中心 郑州 450052
  • 收稿日期:2024-03-09 修回日期:2024-07-24 出版日期:2025-03-01 发布日期:2025-03-01
  • 通讯作者: 魏雪琴
  • 作者简介:魏雪琴，副主任医师，博士，Email：dentistwendy@qq.com
  • 基金资助:
    河南省医学科技攻关计划软科学项目及联合共建项目(LHGJ20220361);河南省科技攻关项目(232102310491)

Mechanism of transferrin-modified liposomal curcumin on proliferation inhibition of oral squamous cell carcinoma

Xueqin Wei(),Kai Ba   

  1. Dept. of Stomatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Received:2024-03-09 Revised:2024-07-24 Online:2025-03-01 Published:2025-03-01
  • Contact: Xueqin Wei
  • Supported by:
    Soft Science Project and Joint Construction Project of Henan Medical Science and Technology Research Plan(LHGJ20220361);Henan Province Science and Technology Research Project(232102310491)

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摘要：

目的 研究转铁蛋白（Tf）修饰的姜黄素（Cur）脂质体（Lips）对口腔鳞状细胞癌细胞株HN4的影响。 方法 制备Cur-Lips以及Tf-Cur-Lips；通过Cur体外释放实验以及大鼠体内药物代谢动力学实验，考察Cur-Lips及Tf-Cur-Lips对Cur体内外代谢的调节作用；用不同浓度的Cur、Cur-Lips及Tf-Cur-Lips溶液处理HN4细胞后，采用细胞计数试剂-8实验检测不同实验组对HN4细胞增殖的影响；实时荧光定量聚合酶链式反应技术检测凋亡相关基因P53和Fas表达水平变化，以探讨Tf修饰对Cur-Lips抑制HN4细胞增殖和凋亡的分子机制。 结果 与Cur相比，Cur-Lips显著延长了Cur的代谢时间；Tf-Cur-Lips能进一步提高Cur的稳定性，延长Cur的代谢时间。与Cur及Cur-Lips相比，Tf-Cur-Lips能显著增强Cur对HN4细胞的增殖抑制，并上调凋亡相关基因P53和Fas的表达。 结论 Tf-Cur-Lips相比于Cur和Cur-Lips，具有更强的抑制口腔鳞状细胞癌细胞株HN4增殖的作用。

关键词: 姜黄素, 脂质体, 转铁蛋白, HN4细胞, 细胞凋亡

Abstract:

Objective This study aimed to investigate the effect of transferrin (Tf)-modified curcumin (Cur)-loaded liposomes (Lips) on the oral squamous cell carcinoma cell line HN4. Methods Cur-Lips and Tf-Cur-Lips were prepared, and their regulatory effects on the internal and external disposal of curcumin were investigated during Cur release in vitro and pharmacokinetics in vivo in rats. Then, HN4 cells were treated with Cur, Cur-Lips, and Tf-Cur-Lips at different concentrations successively, and cell counting kit-8 was used to detect the effects of different experimental groups on HN4 cell proliferation. Finally, the expression levels of apoptosis-related genes P53 and Fas and the molecular mechanism of transferrin modification on Cur-Lips inhibiting the proliferation and apoptosis of HN4 cells were investigated through real-time fluorescence quantitative polymerase chain reaction. Results Compared with Cur, Cur-Lips considerably prolonged metabolic time, and transferrin modification further improved the stability of Cur and prolonged the metabolic time of Cur-Lips. Compared with Cur and Cur-Lips, Tf-Cur-Lips markedly enhanced the inhibitory effect on the HN4 cell proliferation and up-regulated the expression of P53 and Fas. Conclusion Tf-Cur-Lips have a stronger inhibitory effect on oral squamous cell carcinoma cell HN4 than Cur and Cur-Lips.

Key words: curcumin, liposomes, transferrin, HN4 cells, cell apoptosis

中图分类号: 

  • R780.1

表 1

基因引物序列表"

基因引物序列（5’-3’）
GAPDH上游：GACGGCCGCATCTTCTTGTGC
下游：TGCAAATGGCAGCCCTGGTGA
P53上游：CTTTGAGGTGCGTGTTT
下游：CAGTGCTCGCTTAGTGC
Fas上游：GTGATGAAGGGCATGGTTTAG
下游：GCATTTGGTGTTGCTGGTT

表 2

Cur-Lips及Tf-Cur-Lips的粒径和表面电位"

组别粒径/nm分散系数表面电位/mV
Cur-Lips183.0±2.80.19±0.03-28.8±0.3
Tf-Cur-Lips194.0±2.1*0.20±0.05-29.3±0.5

图 1

粒径和电位分布图A：Cur-Lips典型粒径图；B：Tf-Cur-Lips典型粒径图；C：Cur-Lips电位分布图；D：Tf-Cur-Lips电位分布图。"

图 2

扫描电子显微镜照片A：Cur-Lips；B：Tf-Cur-Lips；比例尺：1 μm。"

图 3

Cur体外累积释放率A：Cur；B：Cur-Lips和Tf-Cur-Lips；*：P<0.05。"

图 4

4种浓度下Cur、Cur-Lips及Tf-Cur-Lips对HN4细胞增殖的抑制作用A：处理1 d；B：处理3 d；*：P<0.05。"

图 5

Cur、Cur-Lips及Tf-Cur-Lips对HN4的P53和Fas基因表达的影响*：P<0.05。"

图6

大鼠体内的药物代谢动力学特征图A：Cur；B：Cur-Lips和Tf-Cur-Lips；*：P<0.05。"

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