ALOX5通过p38/ERK/PPARα轴重编程脂质代谢，介导肾细胞癌对舒尼替尼的耐药性
ALOX5 mediates sunitinib resistance in renal cell carcinoma by reprogramming lipid metabolism through the p38/ERK/PPARα axis.
摘要(中文译文)
探讨脂质代谢重编程促进肾细胞癌(RCC)酪氨酸激酶抑制剂(TKIs)耐药的分子机制。建立舒尼替尼耐药肾细胞癌细胞系(786O-R)，并通过转录组测序筛选出调控脂质代谢的关键基因花生四烯酸5-脂氧合酶(ALOX5)。通过数据库及临床样本探讨ALOX5在TKI耐药RCC组织和细胞中的表达及其与RCC患者预后的关系。体外实验探讨ALOX5对RCC细胞恶性生物学行为及舒尼替尼耐药的影响。通过转录组测序及分子实验探讨ALOX5调控脂质代谢的分子机制。通过动物实验探讨抑制ALOX5对786O-R细胞成瘤能力的影响。ALOX5在TKI耐药RCC组织和细胞中表达上调。ALOX5高表达与RCC患者不良预后相关。过表达ALOX5可增强786O-R细胞的增殖、迁移、侵袭及舒尼替尼耐药能力。ALOX5通过p38/ERK/PPARα/CPT1A通路调控脂质代谢，促进786O-R细胞舒尼替尼耐药。抑制ALOX5可抑制786O-R细胞皮下肿瘤生长及肺转移。ALOX5通过p38/ERK/PPARα/CPT1A通路促进脂质代谢，介导RCC舒尼替尼耐药。抑制ALOX5可能成为干预RCC代谢异常及克服靶向治疗耐药的潜在治疗靶点。
Abstract
To investigate the molecular mechanisms of lipid metabolic reprogramming promoting tyrosine kinase inhibitors (TKIs) resistance in renal cell carcinoma (RCC). To establish a sunitinib resistant renal cell carcinoma cell line (786O-R) and screen out arachidonic acid 5-lipoxygenase (ALOX5), a key gene regulating lipid metabolism, by transcriptome sequencing. To explore the expression of ALOX5 in TKI-resistant RCC tissues and cells, and the relationship between ALOX5 expression and the prognosis of RCC patients through databases and clinical samples. To explore the effect of ALOX5 on the malignant biological behavior of RCC cells and drug resistance to sunitinib in vitro. Transcriptome sequencing and molecular experiments were performed to explore the molecular mechanism of ALOX5 regulating lipid metabolism. The effect of ALOX5 inhibition on the tumorigenesis of 786O-R cell was investigated by animal experiments. ALOX5 is upregulated in TKI-resistant RCC tissues and cells. High ALOX5 expression is associated with poor prognosis of patients with RCC. Overexpression of ALOX5 can enhance the proliferation, migration, invasion and sunitinib resistance of 786O-R cell. ALOX5 promotes sunitinib resistance in 786O-R cell by regulating lipid metabolism through the p38/ERK/PPARα/CPT1A pathway. Inhibition of ALOX5 inhibited the growth of subcutaneous tumors and lung metastases in 786O-R cell. ALOX5 mediates sunitinib resistance in RCC by promoting lipid metabolism through the p38/ERK/PPARα/CPT1A pathway. Inhibition of ALOX5 may be a potential therapeutic target for intervention of metabolic abnormalities and overcoming resistance to targeted therapy in RCC.
如何引用
AMA
Sichen Di, Ji Liu, Zhuoran Gu, Chengqi Jin, Junfeng Zhang, Keqiang Li, et al. ALOX5 mediates sunitinib resistance in renal cell carcinoma by reprogramming lipid metabolism through the p38/ERK/PPARα axis.. International immunopharmacology. 2026; doi:10.1016/j.intimp.2026.117006.
APA
Sichen Di, Ji Liu, Zhuoran Gu, Chengqi Jin, Junfeng Zhang, Keqiang Li, et al (2026). ALOX5 mediates sunitinib resistance in renal cell carcinoma by reprogramming lipid metabolism through the p38/ERK/PPARα axis.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.117006
GB/T 7714
Sichen Di, Ji Liu, Zhuoran Gu, Chengqi Jin, Junfeng Zhang, Keqiang Li, et al. ALOX5 mediates sunitinib resistance in renal cell carcinoma by reprogramming lipid metabolism through the p38/ERK/PPARα axis.[J]. International immunopharmacology, 2026 doi:10.1016/j.intimp.2026.117006.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出