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载二氢青蒿素紫杉醇联合川芎嗪胶束通过 DQA 修饰抑制非小细胞肺癌转移。

Inhibiting tumour metastasis by DQA modified paclitaxel plus ligustrazine micelles in treatment of non-small-cell lung cancer.

机构信息

Innovation Center for Traditional Tibetan Medicine Modernization and Quality Control, Medicine College of Tibet University , Lhasa , China.

Traditional Tibetan Medical Research and Study Institute of Regional Traditional Tibetan Medical Hospital , Lhasa , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3465-3477. doi: 10.1080/21691401.2019.1653900.

Abstract

Lung cancer is a kind of malignant tumour characterized as uncontrolled cell growth in lung. These malignant cell growth can spread beyond the lung by process of metastasis into other tissues or parts of the body. In this study, we developed dequalinium (DQA) modified paclitaxel plus ligustrazine micelles to destroy vasculogenic mimicry (VM) channels and inhibit tumour metastasis. assays showed that the targeting micelles with centralized particle size distribution showed not only vigoroso cytotoxicity on A549 cells but also strong inhibition on VM channels and tumour metastasis. Mechanism studies indicated that the DQA modified paclitaxel plus ligustrazine micelles could down-regulate the expressions of VEGF, MMP2, TGF-β1 and E-cadherin in A549 cells. assays indicated that the targeting drug-loaded micelles could enhance the accumulation of chemotherapeutic drugs at tumour sites and exhibit strong tumour inhibitory activity with negligible toxicity. Hence, the DQA modified paclitaxel plus ligustrazine micelles developed in this study may provide a potential strategy for treatment of NSCLC.

摘要

肺癌是一种恶性肿瘤,其特征是肺部的细胞生长失控。这些恶性细胞可以通过转移过程扩散到肺部以外的其他组织或身体部位。在这项研究中,我们开发了癸甲氯铵(DQA)修饰的紫杉醇加川芎嗪胶束,以破坏血管生成拟态(VM)通道并抑制肿瘤转移。 实验表明,具有集中粒径分布的靶向胶束不仅对 A549 细胞表现出强烈的细胞毒性,而且对 VM 通道和肿瘤转移具有强烈的抑制作用。机制研究表明,DQA 修饰的紫杉醇加川芎嗪胶束可以下调 A549 细胞中 VEGF、MMP2、TGF-β1 和 E-钙黏蛋白的表达。 实验表明,靶向载药胶束可以增强化疗药物在肿瘤部位的积累,并表现出强烈的肿瘤抑制活性,而毒性可忽略不计。因此,本研究中开发的 DQA 修饰的紫杉醇加川芎嗪胶束可能为治疗非小细胞肺癌提供了一种潜在策略。

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