Vakhrusheva Olesya, Zhao Fuguang, Markowitsch Sascha Dennis, Slade Kimberly Sue, Brandt Maximilian Peter, Tsaur Igor, Cinatl Jindrich, Michaelis Martin, Efferth Thomas, Blaheta Roman Alexander, Haferkamp Axel, Juengel Eva
Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Department of Urology, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Cells. 2025 Apr 10;14(8):570. doi: 10.3390/cells14080570.
The survival of patients with locally advanced and metastatic bladder cancer (BCa) is persistently low. Hence, new treatment options are urgently needed. Artesunate (ART) a derivative of artemisinin, used in Traditional Chinese Medicine, shows anti-tumor activity extending over a broad spectrum of human cancers. As we have previously shown, ART inhibits growth in cisplatin-sensitive (parental) and cisplatin-resistant BCa cells. However, how ART acts on the metastatic potential of BCa remained unclear. To clarify, we applied ART to parental and cisplatin-resistant RT4, RT112, T24, and TCCSup BCa cell lines. We examined tumor cell adhesion to vascular endothelium and immobilized collagen and evaluated chemotactic activity, migration, and invasive activity of the BCa cells. Adhesion receptors, integrin α and β subtypes, integrin-linked kinase (ILK), and focal adhesion kinase (FAK) were investigated. The functional relevance of integrin expression altered by ART was determined by blocking studies. ART significantly reduced tumor cell adhesion to vascular endothelium and immobilized collagen in parental as well as in cisplatin-resistant BCa cells. Depending on cell type, ART suppressed tumor cell motility and diminished integrin expression (surface and total). Functional blocking of integrins altered by ART reduced cell adhesion and invasion of the BCa cells. Thus, the metastatic potential of parental and cisplatin-resistant BCa cells was significantly inhibited by ART, making it a promising treatment option for patients with advanced or therapy-resistant BCa.
局部晚期和转移性膀胱癌（BCa）患者的生存率一直很低。因此，迫切需要新的治疗方案。青蒿琥酯（ART）是一种青蒿素衍生物，用于传统中药，显示出对多种人类癌症具有抗肿瘤活性。正如我们之前所表明的，ART可抑制顺铂敏感（亲本）和顺铂耐药BCa细胞的生长。然而，ART如何作用于BCa的转移潜能仍不清楚。为了阐明这一点，我们将ART应用于亲本和顺铂耐药的RT4、RT112、T24和TCCSup BCa细胞系。我们检测了肿瘤细胞与血管内皮和固定化胶原蛋白的黏附，并评估了BCa细胞的趋化活性、迁移和侵袭活性。研究了黏附受体、整合素α和β亚型、整合素连接激酶（ILK）和黏着斑激酶（FAK）。通过阻断研究确定了ART改变的整合素表达的功能相关性。ART显著降低了亲本以及顺铂耐药BCa细胞与血管内皮和固定化胶原蛋白的肿瘤细胞黏附。根据细胞类型，ART抑制肿瘤细胞运动并减少整合素表达（表面和总表达）。ART改变的整合素的功能阻断降低了BCa细胞的黏附和侵袭。因此，ART显著抑制了亲本和顺铂耐药BCa细胞的转移潜能，使其成为晚期或治疗耐药BCa患者有前景的治疗选择。
