摘要
背景:癌症相关炎症被认为是肿瘤进展的驱动因素,趋化因子在许多癌症类型的炎症和进展中都是重要的参与者。 CXC趋化因子特别是CXCL8与黑色素瘤生长和转移有关,而其在耐药性中的作用较少。 方法:通过连续暴露于化疗药物产生耐药细胞,分析恶性黑素瘤治疗耐药的机制。 结果:我们报道化学疗法诱导CXCR1 / CXCR2网络中的各种趋化因子通过NF-kB依赖性机制上调。值得注意的是,长期暴露于化疗药达卡巴嗪后选择的耐药性黑素瘤细胞系的分析显示与亲本细胞相比,CXCL8和CXCR2的水平更高,作为耐药性的标志。 CXCR2中和显着提高了对达卡巴嗪在黑素瘤细胞中的敏感性。 结论:这些数据提供了有关驱使黑色素瘤细胞在化疗后存活的原因的见解,从而指出了开发联合药物疗法以对抗黑色素瘤中的化学疗法抗性问题的策略。
关键词: 黑色素瘤,CXCR1,CXCR2,耐药,化疗,NF-κB
Current Molecular Medicine
Title:CXCR1/2 Chemokine Network Regulates Melanoma Resistance to Chemotherapies Mediated by NF-κB
Volume: 17 Issue: 6
关键词: 黑色素瘤,CXCR1,CXCR2,耐药,化疗,NF-κB
摘要: Background: Cancer-related inflammation is recognized as a driver for tumor progression and chemokines are important players in both inflammation and the progression of many cancer types. CXC chemokines, especially CXCL8, have been implicated in melanoma growth and metastasis, while less is known for their roles in drug resistance.
Methods: We generated drug-resistant cells by continuous exposure to chemotherapeutic drugs and analyzed the mechanism(s) of therapy resistance in malignant melanoma.
Results: We report chemotherapies induced upregulation of a variety of chemokines in the CXCR1/CXCR2 network by an NF-κB-dependent mechanism. Notably, analysis of the drug-resistant melanoma cell line selected after prolonged exposure to chemotherapeutic drug dacarbazine revealed higher levels of CXCL8 and CXCR2 compared with parent cells as a signature of drug resistance. CXCR2 neutralization markedly improved sensitivity to dacarbazine in melanoma cells.
Conclusion: These data provide insights into what drives melanoma cells to survive after chemotherapy treatment, thus pointing to strategies for developing combined drug therapies for combating the problem of chemotherapy resistance in melanoma.
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Cite this article as:
CXCR1/2 Chemokine Network Regulates Melanoma Resistance to Chemotherapies Mediated by NF-κB, Current Molecular Medicine 2017; 17 (6) . https://dx.doi.org/10.2174/1566524018666171219100158
DOI https://dx.doi.org/10.2174/1566524018666171219100158 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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