a Department of Clinical and Experimental Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology , University of Florence , Florence , Italy.
b Department of NEUROFARBA , University of Florence , Florence , Italy.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):117-123. doi: 10.1080/14756366.2018.1532419.
Drug combination represents one of the most accredited strategies of cancer therapy able to improve drug efficacy and possibly overcome drug resistance. Among the agents used to complement conventional chemotherapy, carbonic anhydrase IX (CAIX) inhibitors appear as one of the most suitable, as markers of hypoxic and acidic cancer cells which do not respond to chemo- and radiotherapy. We performed preclinical in vitro assays to evaluate whether the SLC-0111 CAIX inhibitor co-operates and potentiates the cytotoxic effects of conventional chemotherapeutic drugs in A375-M6 melanoma cells, MCF7 breast cancer cells, and HCT116 colorectal cancer cells. Here, we demonstrate that the SLC-0111 CAIX inhibitor potentiates cytotoxicity of Dacarbazine and Temozolomide currently used for advanced melanoma treatment. SLC-0111 also increases breast cancer cell response to Doxorubicin and enhances 5-Fluorouracil cytostatic activity on colon cancer cells. These findings disclose the possibility to extend the use of CAIX inhibitors in the combination therapy of various cancer histotypes.
药物联合治疗是癌症治疗中最被认可的策略之一，能够提高药物疗效，并可能克服耐药性。在用于补充常规化疗的药物中，碳酸酐酶 IX（CAIX）抑制剂作为缺氧和酸性癌细胞的标志物，成为最适合的药物之一，这些细胞对化疗和放疗无反应。我们进行了临床前体外检测，以评估 SLC-0111 CAIX 抑制剂是否与常规化疗药物在 A375-M6 黑色素瘤细胞、MCF7 乳腺癌细胞和 HCT116 结肠癌细胞中协同作用并增强其细胞毒性作用。在这里，我们证明 SLC-0111 CAIX 抑制剂增强了目前用于晚期黑色素瘤治疗的达卡巴嗪和替莫唑胺的细胞毒性。SLC-0111 还增加了乳腺癌细胞对多柔比星的反应，并增强了氟尿嘧啶对结肠癌细胞的细胞抑制活性。这些发现揭示了 CAIX 抑制剂在各种癌症组织类型的联合治疗中扩大应用的可能性。
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