Mechanism of astragaloside IV enhancing the sensitivity of non-small cell lung cancer to bevacizumab via the lncRNA-PVT1/miR-361-3p/HMGB1 axis

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2025-09-08 DOI:10.1016/j.imbio.2025.153115

Mingfang Huang, Dewei Wang, Fengxia Chen, Liang Li

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引用次数: 0

Abstract

Objective

This study investigated how astragaloside IV (AST-IV) enhances the responsiveness of non-small cell lung cancer (NSCLC) to bevacizumab (BV) via the lncRNA-PVT1/miR-361-3p/HMBG1 axis.

Methods

Human NSCLC A549 cells were cultured in vitro. oe-NC, A549 cells were transfected with oe-PVT1, oe-HMGB1, mimics NC, and mimics miR for 24 h using transfection reagents and then treated with 50 ng/mL AST-IV and 25 μmol/L BV for 24 h. Expression levels of PVT1, miR-361-3p, and HMGB1 were quantified by RT-qPCR, while protein levels of HMGB1, Ki67, Bax, and Cleaved-caspase-3 were examined through western blot analysis. Proliferation was measured using the CCK-8 assay, and apoptosis was assessed via flow cytometry. The targeting interactions between PVT1 and miR-361-3p, as well as miR-361-3p and HMGB1 were predicted by the BiBiServ2 database and verified by the luciferase reporter assay.

Results

AST-IV and BV-treated A549 cells exhibited significantly inhibited cell proliferation and Ki67/lncRNA-PVT1 expression levels while enhancing apoptosis and upregulating miR-361-3p and Bax and Cleaved-caspase-3. Co-treatment of AST-IV and BV enhanced the sensitivity of A549 cells to BV, further promoted apoptosis, and inhibited cell proliferation. Overexpression of lncRNA-PVT1 down-regulated miR-361-3p levels and partially reversed the promotional effect of AST-IV and BV on the sensitivity of A549 cells to BV. On the basis of overexpression of lncRNA-PVT1, upregulation of miR-361-3p expression significantly increased the sensitivity of A549 cells to BV. Binding interactions between lncRNA-PVT1 and miR-361-3p, as well as miR-361-3p and HMGB1, were confirmed through luciferase assays. Additionally, HMGB1 overexpression counteracted the suppressive effects of AST-IV and BV on A549 cell proliferation and resistance.

Conclusions

AST-IV increased miR-361-3p expression while suppressing HMGB1 via downregulation of lncRNA-PVT1, thereby enhancing BV sensitivity in NSCLC.

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黄芪甲苷通过lncRNA-PVT1/miR-361-3p/HMGB1轴增强非小细胞肺癌对贝伐单抗敏感性的机制

目的：本研究探讨黄芪甲苷（AST-IV）如何通过lncRNA-PVT1/miR-361-3p/HMBG1轴增强非小细胞肺癌（NSCLC）对贝伐单抗（BV）的反应性。方法：体外培养人NSCLC A549细胞。用转染试剂转染e-PVT1、e-HMGB1、mimic NC和mimic miR 24 h，然后用50 ng/mL AST-IV和25 μmol/L BV处理24 h， RT-qPCR检测PVT1、miR-361-3p和HMGB1的表达水平，western blot检测HMGB1、Ki67、Bax和aved-caspase-3的蛋白表达水平。CCK-8法检测细胞增殖，流式细胞术检测细胞凋亡。通过BiBiServ2数据库预测PVT1与miR-361-3p、miR-361-3p与HMGB1之间的靶向相互作用，并通过荧光素酶报告基因检测进行验证。结果：AST-IV和bv处理的A549细胞明显抑制细胞增殖和Ki67/lncRNA-PVT1表达水平，增强细胞凋亡，上调miR-361-3p、Bax和Cleaved-caspase-3。AST-IV与BV共处理可增强A549细胞对BV的敏感性，进一步促进细胞凋亡，抑制细胞增殖。lncRNA-PVT1过表达可下调miR-361-3p水平，部分逆转AST-IV和BV对A549细胞对BV敏感性的促进作用。在lncRNA-PVT1过表达的基础上，上调miR-361-3p表达可显著提高A549细胞对BV的敏感性。lncRNA-PVT1与miR-361-3p以及miR-361-3p与HMGB1之间的结合相互作用通过荧光素酶测定得到证实。HMGB1过表达可抵消AST-IV和BV对A549细胞增殖和耐药的抑制作用。结论：AST-IV上调miR-361-3p表达，同时通过下调lncRNA-PVT1抑制HMGB1，从而增强了BV在NSCLC中的敏感性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.