{"title":"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。","authors":"Zhongqiang Cheng, Lixian Huang, Yanshu Zhang, Kaiyue Yue, Shunmo Jia, Zhijie Fang, Zhiqiang Lin","doi":"10.1186/s12935-025-03908-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>This work suggests that HO-1 is pertinent to acquired CDDP resistance in NPC cells by suppressing oxidative stress and ferroptosis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"302"},"PeriodicalIF":6.0000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337500/pdf/","citationCount":"0","resultStr":"{\"title\":\"Heme oxygenase-1 leads to cisplatin resistance in nasopharyngeal carcinoma by reducing oxidative stress and ferroptosis.\",\"authors\":\"Zhongqiang Cheng, Lixian Huang, Yanshu Zhang, Kaiyue Yue, Shunmo Jia, Zhijie Fang, Zhiqiang Lin\",\"doi\":\"10.1186/s12935-025-03908-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>This work suggests that HO-1 is pertinent to acquired CDDP resistance in NPC cells by suppressing oxidative stress and ferroptosis.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"302\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337500/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03908-6\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03908-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.