2. Academic Validation
  3. Apigenin inhibits recurrent bladder cancer progression by targeting VEGF-β

Apigenin inhibits recurrent bladder cancer progression by targeting VEGF-β

  • Cancer Lett. 2025 Jun 28:620:217676. doi: 10.1016/j.canlet.2025.217676.
Zhen-Duo Shi 1,  Ying Liu 2,  Zi-Qi Tao 3,  Liu Chao 3,  Zheng-Guo Zhang 3,  Fang Sun 3,  Fu-Kang Yuan 3,  Qing-Fang Ma 3,  Zong-Yun Li 3,  Zhe-Sheng Chen 4,  Shao-Yuan Wu 5,  Cong-Hui Han 6
Affiliations

Affiliations

  • 1 School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu, China; Department of Urology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Provincial Engineering Research Center of Cancer Cell Therapy and Translational Medicine, Xuzhou City Engineering Research Center of Cancer Cell Therapy and Translational Medicine, Jiangsu, China; Department of Urology, Peixian People's Hospital, Jiangsu, China.
  • 2 School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu, China; Jiangsu Provincial Engineering Research Center of Cancer Cell Therapy and Translational Medicine, Xuzhou City Engineering Research Center of Cancer Cell Therapy and Translational Medicine, Jiangsu, China.
  • 3 School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu, China.
  • 4 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
  • 5 School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu, China. Electronic address: shaoyuan5@gmail.com.
  • 6 School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu, China; Department of Urology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Provincial Engineering Research Center of Cancer Cell Therapy and Translational Medicine, Xuzhou City Engineering Research Center of Cancer Cell Therapy and Translational Medicine, Jiangsu, China. Electronic address: hanconghuidoctor@vip.qq.com.
PMID: 40185304 DOI: 10.1016/j.canlet.2025.217676
Abstract

Bladder Cancer is a major global health concern with high incidence and mortality rates. Both muscle-invasive bladder Cancer (MIBC) and recurrent non-muscle-invasive bladder Cancer (NMIBC) present significant challenges in treatment. Apigenin, a naturally occurring flavonoid, has shown promise in inhibiting the growth of bladder Cancer cells, however, its therapeutic mechanism remains unclear. Single-cell RNA Sequencing (scRNA-seq) data analysis and drug target screening were performed. Differentially expressed genes (DEGs) and potential therapeutic targets of apigenin were identified. Molecular docking was utilized to evaluate the binding affinity between apigenin and VEGF-β. In vitro assays were conducted to evaluate the association of VEGF-β and apigenin. Drug target screening identified 51 common targets between apigenin and bladder Cancer, with VEGF-β emerging as a dominant gene. Molecular docking confirmed a high binding affinity between apigenin and VEGF-β. VEGF-β was significantly upregulated in fibroblasts from recurrent bladder Cancer, correlating with increased tumor malignancy. Enhanced cell communication in VEGF-β-positive fibroblasts contributed to tumor progression. In vitro experiments demonstrated that VEGF-β promotes tumor cell proliferation, migration, and invasion. Apigenin significantly inhibits bladder Cancer progression by targeting VEGF-β. The upregulation of VEGF-β in fibroblasts from recurrent bladder Cancer highlights its potential as a diagnostic marker and therapeutic target. This study underscores the promise of apigenin as a chemopreventive and therapeutic agent for recurrent bladder Cancer.

Keywords

Apigenin; Chemopreventive agent; Drug target screening; Single-cell RNA sequencing.

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