FoxG1/BNIP3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma

IF 4.5 2区医学 Q1 ONCOLOGY Cancer Science Pub Date : 2024-06-26 DOI:10.1111/cas.16242

Baolong Pan, Yan Li, Huiyun Han, Lu Zhang, Xuemei Hu, Yanyu Pan, Zhuohui Peng

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Abstract

Cisplatin (CDDP) is a commonly used chemotherapeutic for osteosarcoma (OS) patients, and drug resistance remains as a major hurdle to undermine the treatment outcome. Here, we investigated the potential involvement of FoxG1 and BNIP3 in CDDP resistance of OS cells. FoxG1 and BNIP3 expression levels were detected in the CDDP-sensitive and CDDP-resistant OS tumors and cell lines. Mitophagy was observed through transmission electron microscope analysis. The sensitivity to CDDP in OS cells upon FoxG1 overexpression was examined in cell and animal models. We found that FoxG1 and BNIP3 showed significant downregulation in the CDDP-resistant OS tumor samples and cell lines. CDDP-resistant OS tumor specimens and cells displayed impaired mitophagy. FoxG1 overexpression promoted BNIP3 expression, enhanced mitophagy in CDDP-resistant OS cells, and resensitized the resistant cells to CDDP treatment in vitro and in vivo. Our data highlighted the role of the FoxG1/BNIP3 axis in regulating mitophagy and dictating CDDP resistance in OS cells, suggesting targeting FoxG1/BNIP3-dependent mitophagy as a potential strategy to overcome CDDP resistance in OS.

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FoxG1/BNIP3轴促进骨肉瘤的有丝分裂并减弱顺铂耐药性

顺铂（CDDP）是骨肉瘤（OS）患者常用的化疗药物，耐药性仍然是影响治疗效果的主要障碍。在此，我们研究了FoxG1和BNIP3在OS细胞CDDP耐药性中的潜在参与。我们在对CDDP敏感和耐药的OS肿瘤和细胞系中检测了FoxG1和BNIP3的表达水平。通过透射电子显微镜分析观察了细胞的有丝分裂。在细胞和动物模型中研究了FoxG1过表达时OS细胞对CDDP的敏感性。我们发现，FoxG1和BNIP3在CDDP耐药的OS肿瘤样本和细胞系中表现出明显的下调。CDDP耐药OS肿瘤标本和细胞的有丝分裂功能受损。FoxG1的过表达促进了BNIP3的表达，增强了CDDP耐药OS细胞的有丝分裂，并使耐药细胞在体外和体内对CDDP治疗重新敏感。我们的数据强调了FoxG1/BNIP3轴在调控OS细胞有丝分裂和决定CDDP耐药性中的作用，表明靶向FoxG1/BNIP3依赖的有丝分裂是克服OS中CDDP耐药性的一种潜在策略。

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来源期刊

Cancer Science 医学-肿瘤学

自引率

3.50%

发文量

406

审稿时长

2 months

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.

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