Yang Chao, Liu Yunjiang, Gai Lingyun, Zhang Ziteng, Zhang Yanshou, Zhang Geng, Du Kaiye, Gao Chao
Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
PLoS One. 2025 Aug 4;20(8):e0329490. doi: 10.1371/journal.pone.0329490. eCollection 2025.
Breast cancer continues to be a predominant cause of female mortality globally, characterized by limited therapeutic options and substantial adverse effects. Artesunate (ART), a traditional Chinese medicine approved by the FDA for malaria treatment, has demonstrated potential anticancer properties against breast cancer. However, the underlying molecular mechanisms remain incompletely elucidated. This study posits that the antitumor efficacy of artesunate may be mediated through the regulation of the lncRNA TUG1/miR-145-5p/HOXA5 axis.
A comprehensive array of in vitro assays was employed to investigate the proposed molecular pathway, including CCK-8 proliferation assay, EdU incorporation assay, Transwell invasion assay, scratch wound healing assay, TUNEL apoptosis assay, and dual-luciferase reporter assay. Additionally, Western blot analysis, quantitative real-time PCR (qPCR), and plasmid transfection techniques were utilized to validate the findings.
The results revealed that artesunate exerted a dose-dependent inhibitory effect on breast cancer cell proliferation. This was accompanied by the down-regulation of HOXA5, WNT, β-catenin, Fizz1, and Arg-1, implicating the involvement of the WNT/β-catenin signaling pathway. Furthermore, artesunate significantly modulated the expression levels of lncRNA TUG1, miR-145-5p, and HOXA5, suggesting a mechanistic role of the lncRNA TUG1 pathway in its anticancer activity.
These findings indicate that artesunate may inhibit breast cancer progression through the lncRNA TUG1/miR-145-5p/HOXA5 axis, highlighting its potential as a promising therapeutic candidate for future clinical trials in cancer therapy.
乳腺癌仍然是全球女性死亡的主要原因，其特点是治疗选择有限且副作用严重。青蒿琥酯（ART）是一种经美国食品药品监督管理局（FDA）批准用于治疗疟疾的传统中药，已显示出对乳腺癌具有潜在的抗癌特性。然而，其潜在的分子机制仍未完全阐明。本研究假设青蒿琥酯的抗肿瘤功效可能是通过调节lncRNA TUG1/miR-145-5p/HOXA5轴来介导的。
采用一系列体外实验来研究所提出的分子途径，包括CCK-8增殖实验、EdU掺入实验、Transwell侵袭实验、划痕伤口愈合实验、TUNEL凋亡实验和双荧光素酶报告实验。此外，利用蛋白质免疫印迹分析、定量实时PCR（qPCR）和质粒转染技术来验证研究结果。
结果显示，青蒿琥酯对乳腺癌细胞增殖具有剂量依赖性抑制作用。这伴随着HOXA5、WNT、β-连环蛋白、Fizz1和Arg-1的下调，表明WNT/β-连环蛋白信号通路参与其中。此外，青蒿琥酯显著调节lncRNA TUG1、miR-145-5p和HOXA5的表达水平，表明lncRNA TUG1途径在其抗癌活性中具有机制性作用。
这些发现表明，青蒿琥酯可能通过lncRNA TUG1/miR-145-5p/HOXA5轴抑制乳腺癌进展，突出了其作为未来癌症治疗临床试验中有前景治疗候选药物的潜力。
