Abstract

Anti-breast cancer action of novel human carbonic anhydrase IX (hCA IX) inhibitor BSM-0004 has been investigated using in vitro and in vivo models of breast cancer. BSM-0004 was found to be a potent and selective hCA IX inhibitor with a Ki value of 96 nM. In vitro anticancer effect of BSM-0004 was analysed against MCF 7 and MDA-MA-231 cells, BSM-0004 exerted an effective cytotoxic effect under normoxic and hypoxic conditions, inducing apoptosis in MCF 7 cells. Additionally, this compound significantly regulates the expression of crucial biomarkers associated with apoptosis. The investigation was extended to confirm the efficacy of this hCA IX inhibitor against in vivo model of breast cancer. The results specified that the treatment of BSM-0004 displayed an effective in vivo anticancer effect, reducing tumour growth in a xenograft cancer model. Hence, our investigation delivers an effective anti-breast cancer agent that engenders the anticancer effect by inhibiting hCA IX.

摘要

已经使用体外和体内乳腺癌模型研究了新型人碳酸酐酶 IX (hCA IX) 抑制剂 BSM-0004 的抗乳腺癌作用。BSM-0004 被发现是一种有效的选择性 hCA IX 抑制剂，Ki 值为 96 nM。分析了 BSM-0004 对 MCF 7 和 MDA-MA-231 细胞的体外抗癌作用，BSM-0004 在常氧和缺氧条件下发挥有效的细胞毒作用，诱导 MCF 7 细胞凋亡。此外，该化合物显着调节与细胞凋亡相关的关键生物标志物的表达。研究扩展到确认这种 hCA IX 抑制剂对体内乳腺癌模型。结果表明，BSM-0004 的治疗显示出有效的体内抗癌作用，可减少异种移植癌症模型中的肿瘤生长。因此，我们的研究提供了一种有效的抗乳腺癌药物，通过抑制 hCA IX 产生抗癌作用。