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已发表论文
新型 Rho 激酶抑制剂法舒地尔衍生物法舒地尔 - D - 6h 通过调节三阴性乳腺癌中的黏着连接信号通路来阻止肿瘤进展
Authors Liang J, Tang M, Wang L
Received 13 June 2025
Accepted for publication 28 November 2025
Published 8 January 2026 Volume 2026:18 547003
DOI https://doi.org/10.2147/BCTT.S547003
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Pranela Rameshwar
Jinghui Liang,1 Mu Tang,2 Lieliang Wang2
1Department of Comprehensive Radiotherapy, Jiangxi Cancer Hospital & Institute, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, Nanchang City, Jiangxi Province, People’s Republic of China
Correspondence: Lieliang Wang, Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, 518 East Beijing Road, 518 East Beijing Road, Nanchang City, Jiangxi Province, People’s Republic of China, Email zoya1302@163.com
Background: Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options. Rho-associated coiled-coil containing protein kinase (ROCK) signaling is a promising target, known to drive tumor progression through cytoskeletal remodelling and epithelial-mesenchymal transition (EMT). However, its role in disrupting epithelial integrity via adherens and tight junctions in TNBC remains underexplored. Fasudil-D-6h is a novel derivative of the clinically approved ROCK inhibitor fasudil. This study investigates the anti-tumor efficacy of fasudil-D-6h and its novel mechanism of action in TNBC.
Methods: The effects of fasudil-D-6h and the reference inhibitor HA-1100 on cell proliferation (CCK-8) and apoptosis (flow cytometry) were assessed in MDA-MB-231 and MCF-7 cells. Transcriptome sequencing of fasudil-D-6h-treated MDA-MB-231 cells identified differentially expressed genes (DEGs) and enriched pathways. A protein-protein interaction (PPI) network was constructed. The in vivo efficacy was evaluated in a nude mouse model of subcutaneous MDA-MB-231 tumors. qRT–PCR and Western blotting validated the expression of ROCK1/2 and key adherens junction pathway components (Cdc42, Rac3, Src, ZO-1, Occludin, Claudin-1).
Results: Fasudil-D-6h significantly inhibited proliferation and induced apoptosis in TNBC cells. Transcriptomic analysis revealed 8,092 DEGs, with significant enrichment in the adherens junction pathway. Accordingly, fasudil-D-6h treatment in vitro and in vivo significantly downregulated ROCK1/2 and robustly upregulated the expression of CDC42, RAC3, SRC, ZO-1, OCCLUDIN, and CLAUDIN-1. In the mouse model, fasudil-D-6h treatment led to a significant reduction in tumor mass and volume.
Discussion: Our findings demonstrate that the novel ROCK inhibitor fasudil-D-6h exerts potent anti-tumor effects in TNBC. Its mechanism of action is distinctively linked to the restoration of genes critical to adherens and tight junction integrity. Given its derivation from the clinically viable fasudil, fasudil-D-6h presents a strong translational potential as a novel therapeutic agent for TNBC.
Keywords: ROCK inhibitor, fasudil-D-6h, triple-negative breast cancer, adherens junction, breast cancer signalling pathway
1Department of Comprehensive Radiotherapy, Jiangxi Cancer Hospital & Institute, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, Nanchang City, Jiangxi Province, People’s Republic of China
Correspondence: Lieliang Wang, Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, 518 East Beijing Road, 518 East Beijing Road, Nanchang City, Jiangxi Province, People’s Republic of China, Email zoya1302@163.com
Background: Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options. Rho-associated coiled-coil containing protein kinase (ROCK) signaling is a promising target, known to drive tumor progression through cytoskeletal remodelling and epithelial-mesenchymal transition (EMT). However, its role in disrupting epithelial integrity via adherens and tight junctions in TNBC remains underexplored. Fasudil-D-6h is a novel derivative of the clinically approved ROCK inhibitor fasudil. This study investigates the anti-tumor efficacy of fasudil-D-6h and its novel mechanism of action in TNBC.
Methods: The effects of fasudil-D-6h and the reference inhibitor HA-1100 on cell proliferation (CCK-8) and apoptosis (flow cytometry) were assessed in MDA-MB-231 and MCF-7 cells. Transcriptome sequencing of fasudil-D-6h-treated MDA-MB-231 cells identified differentially expressed genes (DEGs) and enriched pathways. A protein-protein interaction (PPI) network was constructed. The in vivo efficacy was evaluated in a nude mouse model of subcutaneous MDA-MB-231 tumors. qRT–PCR and Western blotting validated the expression of ROCK1/2 and key adherens junction pathway components (Cdc42, Rac3, Src, ZO-1, Occludin, Claudin-1).
Results: Fasudil-D-6h significantly inhibited proliferation and induced apoptosis in TNBC cells. Transcriptomic analysis revealed 8,092 DEGs, with significant enrichment in the adherens junction pathway. Accordingly, fasudil-D-6h treatment in vitro and in vivo significantly downregulated ROCK1/2 and robustly upregulated the expression of CDC42, RAC3, SRC, ZO-1, OCCLUDIN, and CLAUDIN-1. In the mouse model, fasudil-D-6h treatment led to a significant reduction in tumor mass and volume.
Discussion: Our findings demonstrate that the novel ROCK inhibitor fasudil-D-6h exerts potent anti-tumor effects in TNBC. Its mechanism of action is distinctively linked to the restoration of genes critical to adherens and tight junction integrity. Given its derivation from the clinically viable fasudil, fasudil-D-6h presents a strong translational potential as a novel therapeutic agent for TNBC.
Keywords: ROCK inhibitor, fasudil-D-6h, triple-negative breast cancer, adherens junction, breast cancer signalling pathway