通过HPX-MAPK通路促进肝细胞癌中的伦瓦替尼抗药性
Jinlu Han1, Chen Wang1, Yun Song1
1Department of Gastroenterology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, China.
Ecotoxicology and environmental safety
|August 26, 2025
概括
通过降低HPX基因,环境酸盐可能导致肝细胞癌 (HCC) 的伦瓦替尼抗性. 恢复HPX显示在HCC治疗中克服药物耐药性的潜力.
科学领域:
- 肝胆医学 肝胆医学
- 环境毒理学
- 分子瘤学
背景情况:
- 在治疗肝细胞癌 (HCC) 方面,伦瓦替尼布耐药性是一个重大挑战.
- 环境酸盐,常见的增塑剂在HCC治疗耐药性的作用尚不清楚.
研究的目的:
- 调查酸盐暴露与林瓦提尼布耐药性之间的潜在关联.
- 确定参与这种抵抗机制的关键基因和分子途径.
主要方法:
- 综合网络毒理学,分子对接和转录组分析.
- 确定了与酸盐相关的伦瓦替尼抗性基因 (PLRGs),并构建了一个预后风险模型.
- 使用功能性测试,西式涂抹和体内小鼠模型进行验证.
主要成果:
- 确定了40个PLRG,基于包括HPX在内的8个基因进行了验证的风险模型.
- 在HCC组织和耐药细胞系中发现HPX的下调,与特定的酸盐相互作用.
- 过度表达HPX抑制了HCC的进展和伦瓦替尼的耐药性,而酸盐暴露则激活了MAPK通路,而HPX则抑制了该通路.
结论:
- 通过HPX- MAPK信号轴,酸盐暴露有助于HCC的伦瓦替尼抗性.
- 作为预后生物标志物和治疗标,HPX在HCC中具有克服伦瓦替尼抗性的潜力.
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