Acidic pH of Tumor Microenvironment Enhances Cytotoxicity of the Disulfiram/Cu2+ Complex to Breast and Colon Cancer Cells
Acidic pH of Tumor Microenvironment Enhances Cytotoxicity of the Disulfiram/Cu2+ Complex to Breast and Colon Cancer Cells
复制标题
DOI：
10.1159/000353915
复制
发表时间：
2013-01-01
期刊：
影响因子：
3.3
通讯作者：
Smarda, Jan
中科院分区：
文献类型：
--
作者：
Navratilova, Jarmila;Hankeova, Tereza;Smarda, Jan
背景：癌细胞对化疗药物的耐药性是癌症患者治疗失败的主要原因。肿瘤细胞的耐药性可以通过肿瘤微生物学的特定特征，例如氧耗尽（缺氧）、葡萄糖/能量剥夺和酸中毒而显著改变。方法：研究酸性肿瘤样微环境对安妥布（双硫仑，DSF）/Cu ~（2+）复合物对MCF-7乳腺癌细胞和HT-29结肠癌细胞的细胞毒作用的影响。结果：我们发现，酸性pH值显着增强DSF/Cu 2+复合物对乳腺癌和结肠癌细胞的毒性。这种现象与细胞代谢的变化、Akt激酶和NF κ B活性的改变以及活性氧产生的增加有关。结论：肿瘤微载体的特定pH值可增强DSF/Cu ~（2+）对乳腺癌和结肠癌细胞的杀伤作用。版权所有（C）2013 S.Karger AG，巴塞尔
Background: Resistance of cancer cells to chemotherapeutic agents is a major cause of treatment failure in patients with cancer. The drug resistance of tumor cells can be significantly modified by specific features of tumor microenvironnnent, such as oxygen depletion (hypoxia), glucose/energy deprivation and acidosis. Methods:The effects of acidic tumor-like microenvironment on cytotoxicity of antabuse (disulfiram, DSF)/ Cu2+ complexes to MCF-7 breast carcinoma and HT-29 colon carcinoma cells were studied. Results: We show that acidic pH significantly potentiates toxicity of DSF/Cu2+ complex to breast and colon cancer cells. This phenomenon is associated with changes in cell metabolism, altered Akt kinase and NFKB activity and increased reactive oxygen species production. Conclusion: Specific pH of tumor microenvironnnent enhances cytotoxicity of DSF/Cu2+ to breast and colon cancer cells. Copyright (C) 2013 S.Karger AG, Basel