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ASPH 失调细胞死亡,并诱导肝细胞癌中的化学抵抗

Jingtao Li¹, Guocai Zhong¹, Fengli Hu²

¹Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, PR China.

|December 20, 2024

概括

亚斯巴酸β-基酶 (ASPH) 通过阻断铁亡,驱动肝细胞癌 (HCC) 的生长和 sorafenib 耐药性. 沉默ASPH使HCC细胞对sorafenib敏感,促进细胞死亡和抑制转移.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症研究癌症研究

背景情况:

肝细胞癌 (HCC) 对索拉费尼布等常规疗法表现出耐药性,需要新的治疗策略.
向治疗和免疫疗法在改善HCC患者结局方面表现出有限的有效性.
诱导癌细胞死亡仍然是HCC治疗的关键目标.

研究的目的:

调查阿斯巴酸β-基酶 (ASPH) 在HCC进展和索拉芬尼布耐药性中的作用.
探索针对ASPH在HCC治疗中与索拉芬尼结合治疗的治疗潜力.

主要方法:

评估了HCC中的ASPH表达及其与临床结果的相关性.
利用基因淘汰 (KO) 和沉默技术来操纵HCC细胞中的ASPH水平.
研究了涉及SQSTM1/P62和SLC7A11-GPX4轴的分子机制.
使用HCC.vivo小鼠模型验证的结果.

主要成果:

在HCC中高ASPH表达促进了扩散,迁移,入侵,并预测索拉费尼布治疗患者的不良结果.
ASPH通过SQSTM1/P62上调自,同时通过SLC7A11-GPX4轴抑制铁化.
ASPH淘汰赛 (KO) 通过减弱自和促进亡和铁亡,使HCC细胞对sorafenib敏感.
联合ASPH沉默和索拉芬尼治疗抑制了瘤生长,转移和茎在体内.

结论:

ASPH在促进HCC生长,转移和对索拉费尼布的耐药性方面发挥着关键作用.
针对ASPH与sorafenib结合的向显示出显著的抗瘤疗效.
抑制ASPH代表了一种有前途的治疗策略,用于克服HCC中索拉芬尼抗性.

关键词:

亚斯巴甜酸β-氧化酶是一种酸盐.肝细胞癌是肝细胞癌.转移转移转移转移索拉费尼布 (Sorafenib) 是一种

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