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基于p53/ARTS介导的线粒体凋亡，透明质酸修饰的脂质体用于熊果酸靶向递送治疗肺癌

Hyaluronic Acid-modified Liposomes for Ursolic Acid-targeted Delivery Treat Lung Cancer Based on p53/ARTS-mediated Mitochondrial Apoptosis.

作者信息

Ma TingTing, Zhou Jiasi, Li Jiajie, Chen Qi

机构信息

Department of Infectious Diseases, Ningbo Yinzhou No.2 Hospital, Ningbo, China.

Department of Respiratory and Critical Care Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, China.

出版信息

Iran J Pharm Res. 2023 Apr 7;22(1):e131758. doi: 10.5812/ijpr-131758. eCollection 2023 Jan-Dec.

DOI:10.5812/ijpr-131758
PMID:38116552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10728842/
Abstract

BACKGROUND

Chemotherapy drugs can cause drug resistance and other problems when treating lung cancer, which leads to treatment failure. Ursolic acid (UA) is used in formulations based on traditional Chinese medicine. UA has excellent anti-tumor effects, but they are limited by solubility and non-specificity to tumor cells.

OBJECTIVES

To overcome these issues, we created a novel hyaluronic acid (HA)-targeted liposome system for delivering UA (HA-Lipo/UA) to explore the targeting and anti-tumor effects of UA.

METHODS

We constructed the HA-Lipo/UA delivery system by the thin film hydration method. The uptake and localization of UA were detected by flow cytometry and microscope. Cell proliferation of A549 cells was detected by MTT assays. Apoptosis and reactive oxygen species (ROS) expression of A549 cells were also evaluated after being treated with HA-Lipo/UA. Western blot analysis evaluated the anti-tumor mechanism of HA-Lipo/UA.

RESULTS

HA-Lipo/UA exhibited favorable targeting of the cluster of differentiation (CD)44-overexpressing A549 cells. HA-Lipo/UA exhibited significant inhibition of the proliferation of A549 cells and induced their apoptosis compared with the corresponding monotherapies. HA-Lipo/UA induced overexpression of reactive oxygen species and upregulated expression of p53 and apoptosis-related protein in the transforming growth factor-β signaling (ARTS) pathway, which induced cytochrome-c release, activation of caspase-3, and promoted mitochondrial apoptosis in A549 cells.

CONCLUSIONS

Taken together, these data suggested that HA-Lipo/UA could be used to target tumor cells.

摘要

背景

化疗药物在治疗肺癌时会导致耐药性等问题，从而导致治疗失败。熊果酸（UA）用于基于传统中药的制剂中。UA具有出色的抗肿瘤作用，但受到溶解度和对肿瘤细胞非特异性的限制。

目的

为克服这些问题，我们创建了一种新型的透明质酸（HA）靶向脂质体系统来递送UA（HA-Lipo/UA），以探索UA的靶向性和抗肿瘤作用。

方法

我们通过薄膜水化法构建了HA-Lipo/UA递送系统。通过流式细胞术和显微镜检测UA的摄取和定位。采用MTT法检测A549细胞的增殖情况。用HA-Lipo/UA处理A549细胞后，还评估了其凋亡和活性氧（ROS）表达。蛋白质免疫印迹分析评估了HA-Lipo/UA的抗肿瘤机制。

结果

HA-Lipo/UA对过表达分化簇（CD）44的A549细胞表现出良好的靶向性。与相应的单一疗法相比，HA-Lipo/UA对A549细胞的增殖具有显著抑制作用并诱导其凋亡。HA-Lipo/UA诱导活性氧过表达，并上调转化生长因子-β信号（ARTS）通路中p53和凋亡相关蛋白的表达，从而诱导细胞色素c释放、半胱天冬酶-3激活，并促进A549细胞的线粒体凋亡。

结论

综上所述，这些数据表明HA-Lipo/UA可用于靶向肿瘤细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/9ec79aed1552/ijpr-22-1-131758-i006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/ebc02febd704/ijpr-22-1-131758-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/78b1202d8175/ijpr-22-1-131758-i001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/d9d3da4def8b/ijpr-22-1-131758-i002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/79d59788e66f/ijpr-22-1-131758-i003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/42e51d56b6a1/ijpr-22-1-131758-i004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/afa9996ca429/ijpr-22-1-131758-i005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/9ec79aed1552/ijpr-22-1-131758-i006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/ebc02febd704/ijpr-22-1-131758-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/78b1202d8175/ijpr-22-1-131758-i001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/d9d3da4def8b/ijpr-22-1-131758-i002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/79d59788e66f/ijpr-22-1-131758-i003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/42e51d56b6a1/ijpr-22-1-131758-i004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/afa9996ca429/ijpr-22-1-131758-i005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1539/10728842/9ec79aed1552/ijpr-22-1-131758-i006.jpg

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