血红素加氧酶-1通过减少氧化应激和铁下垂导致鼻咽癌顺铂耐药。

IF 6 2区 医学 Q1 ONCOLOGY
Zhongqiang Cheng, Lixian Huang, Yanshu Zhang, Kaiyue Yue, Shunmo Jia, Zhijie Fang, Zhiqiang Lin
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引用次数: 0

摘要

背景:鼻咽癌是一种死亡率高的恶性肿瘤。本研究探讨血红素加氧酶-1 (HO-1)在鼻咽癌顺铂耐药中的作用。方法:观察CDDP对两种鼻咽癌细胞株HK1和C666-1的时间依赖性作用。通过将亲本细胞暴露于浓度增加的CDDP中,建立了抗CDDP细胞。亲本细胞用HO-1诱导剂Hemin处理,抗性细胞用HO-1抑制剂ZnPP处理,探讨HO-1活性对鼻咽癌细胞系CDDP抗性的影响。用Erastin验证铁沉对细胞CDDP敏感性的影响。在小鼠异种移植肿瘤模型中进行平行设置以进行体内验证。结果:CDDP在48 h内对鼻咽癌细胞的生长和移动性有时间依赖性,但48 h后细胞毒性不再显著增强。HO-1在CDDP处理后的细胞中表达上调,与获得性CDDP抗性相关。在亲代细胞中诱导HO-1活性可以保护细胞免受氧化损伤、凋亡和铁凋亡,而用ZnPP抑制HO-1活性可以恢复CDDP对耐药细胞的治疗效果。此外,Erastin处理也恢复了CDDP对耐药细胞的细胞毒性。在携带异种移植物肿瘤的小鼠中,用ZnPP或Erastin治疗均可削弱肿瘤的生长和重量。结论:HO-1通过抑制氧化应激和铁凋亡参与鼻咽癌细胞获得性CDDP耐药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Heme oxygenase-1 leads to cisplatin resistance in nasopharyngeal carcinoma by reducing oxidative stress and ferroptosis.

Background: Nasopharyngeal carcinoma (NPC) is a malignancy with high a mortality rate. This study investigates the impact of heme oxygenase-1 (HO-1) in cisplatin (CDDP) resistance in NPC.

Methods: The time-dependent effect of CDDP on two NPC cell lines (HK1 and C666-1) were investigated. CDDP-resistant cells were established by exposing the parental cells to increasing concentrations of CDDP. Parental cells received treatment of the HO-1 inducer Hemin while resistant cells received treatment of the HO-1 inhibitor ZnPP to explore the influence of HO-1 activity on CDDP resistance in NPC cell lines. Erastin was used to verify the effect of ferroptosis on CDDP sensitivity in cells. Parallel settings were performed in mouse xenograft tumor models for in vivo validation.

Results: CDDP time-dependently reduced growth and mobility of NPC cells within the initial 48 h, but the cytotoxicity was no longer significantly enhanced afterward. HO-1 was upregulated in cells after CDDP treatment, showing correlation with acquired CDDP resistance. Inducing HO-1 activity in parental cells protected cells from oxidative damage, apoptosis, and ferroptosis, while suppressing HO-1 activity using ZnPP restored the therapeutic efficacy of CDDP in drug resistant cells. Moreover, the Erastin treatment also restored the cytotoxicity of CDDP to the resistant cells. In mice bearing xenograft tumors, treatment with either ZnPP or Erastin weakened the growth and weight of tumors.

Conclusion: This work suggests that HO-1 is pertinent to acquired CDDP resistance in NPC cells by suppressing oxidative stress and ferroptosis.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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