Zhou Changkuo, Wang Ganyu, Jing Weiqiang, Tan Xuejie, Guo Hu
Department of Urology, Qilu Hospital, Shandong University, Jinan, China.
Department of Pediatric Surgery, Qilu Hospital, Shandong University, Jinan, China.
Front Pharmacol. 2021 Feb 23;12:618668. doi: 10.3389/fphar.2021.618668. eCollection 2021.
Bladder cancer is the most common malignant urinary system tumor. Chemotherapy is frequently used as a treatment regimen for patients with bladder cancer, however, new and effective drugs for bladder cancer need to be developed. The present study examined the effects and mechanisms of Ag-SP-DNC, a silver and singly-protonated dehydronorcantharidin complex, on bladder cancer and . It was identified that Ag-SP-DNC suppressed cell proliferation and induced apoptosis in bladder cancer cells , a suppression associated with G0/G1 phase arrest and elevated intracellular reactive oxygen species (ROS) levels. Furthermore, Ag-SP-DNC enhanced the cleaved caspase-3 levels, disrupted the mitochondrial transmembrane potential balance, and induced intracellular calcium overload. The Ag-SP-DNC-induced bladder cancer cell apoptosis was significantly decreased following treatment with a broad caspase inhibitor, zVAD-fmk. In addition, treatment of MB49 tumor-bearing mice with Ag-SP-DNC significantly inhibited tumor growth and decreased the anti-apoptosis and cell cycle promotion protein levels in the tumor. The results of the present study suggested that Ag-SP-DNC elicits a strong anticancer effect against bladder cancer, and can therefore be used as a promising treatment for bladder cancer.
膀胱癌是泌尿系统最常见的恶性肿瘤。化疗是膀胱癌患者常用的治疗方案，然而，仍需要开发治疗膀胱癌的新型有效药物。本研究检测了银与单质子化去氢斑蝥素复合物（Ag-SP-DNC）对膀胱癌的作用及其机制。研究发现，Ag-SP-DNC可抑制膀胱癌细胞增殖并诱导其凋亡，这种抑制作用与G0/G1期阻滞及细胞内活性氧（ROS）水平升高有关。此外，Ag-SP-DNC可提高裂解的半胱天冬酶-3水平，破坏线粒体跨膜电位平衡，并诱导细胞内钙超载。用广谱半胱天冬酶抑制剂zVAD-fmk处理后，Ag-SP-DNC诱导的膀胱癌细胞凋亡明显减少。此外，用Ag-SP-DNC处理携带MB49肿瘤的小鼠，可显著抑制肿瘤生长，并降低肿瘤中抗凋亡和促进细胞周期蛋白的水平。本研究结果表明，Ag-SP-DNC对膀胱癌具有强大的抗癌作用，因此有望用于膀胱癌的治疗。
