Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells
Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells
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DOI：
10.1016/j.bbrc.2014.03.047
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发表时间：
2014-04-18
影响因子：
3.1
通讯作者：
Huang, Yunchao
中科院分区：
文献类型：
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作者：
Duan, Lincan;Shen, Hongmei;Huang, Yunchao
非小细胞肺癌（NSCLC）是全球男性和女性癌症相关死亡的最常见原因。最近，双硫仑被报道能够抑制胶质母细胞瘤、前列腺癌或乳腺癌细胞增殖。在这项研究中，双硫仑和铜对NSCLC细胞生长的协同作用进行了研究。采用MTT法和细胞周期分析法检测药物对肿瘤细胞增殖的抑制作用。使用液体集落形成和肿瘤球体形成测定来评估它们对癌细胞集落形成的作用。实时荧光定量PCR检测肿瘤干细胞相关基因mRNA水平。我们发现双硫仑或铜单独在体外不能有效抑制NSCLC细胞增殖。然而，铜的存在显著增强了双硫仑对NSCLC细胞生长的抑制作用，表明双硫仑和铜之间存在协同效应。细胞周期分析显示双硫仑/铜络合物可使NSCLC细胞周期阻滞于G2/M期。此外，双硫仑/铜显着增加顺铂在NSCLC细胞中的敏感性通过MTT法测试。液体集落形成实验显示铜显著增强双硫仑对NSCLC细胞集落形成能力的抑制作用。双硫仑联合铜可显著抑制NSCLC细胞球体形成，并抑制肺癌干细胞相关基因mRNA表达。我们的数据表明双硫仑/铜络合物单独或与其他化疗药物联合是NSCLC患者的潜在治疗策略。(C)2014爱思唯尔公司All rights reserved.
Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-y1)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients. (C) 2014 Elsevier Inc. All rights reserved.