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在胃癌细胞中,ADAM9通过DNA损伤反应途径调解了Cisplatin耐药性

Xiao-Yu Zhang^1,2, Chan-Yuan Zhao¹, Jia-Ming Dong¹

¹Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Medical oncology (Northwood, London, England)

|March 20, 2025

概括

在胃癌中ADAM9的高表达通过提升通过ATM-CHK2通路的DNA修复来促进化疗耐药性,这表明ADAM9是克服西斯普拉丁耐药性的潜在治疗标.

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:

胃癌是全球普遍存在的恶性瘤,化学疗法耐药性显著影响患者的治疗结果.
化疗耐药性通常与瘤细胞内增强的DNA修复机制有关.
ADAM9 (一种分解蛋白和金属蛋白酶域-9) 涉及各种癌症过程,包括耐药性.

研究的目的:

为了研究ADAM9在胃癌中对西斯普拉丁耐药性的作用.
阐明ADAM9介导的化疗耐药性的潜在分子机制.

主要方法:

对胃癌组织中ADAM9表达的分析及其与临床病理因素和预后的相关性.
在具有不同ADAM9表达水平的胃癌细胞中评估青的敏感性,DNA损伤和DNA损伤修复蛋白 (ATM,CHK2,γ-H2AX) 的表达.
对胃癌细胞中ADAM9表达的选择性干扰,以评估其对西斯普拉丁耐药性的影响.

主要成果:

在胃癌组织中ADAM9的高表达与不良的临床病理因素和不良预后相关.
较高的ADAM9表达降低了思普拉丁的敏感性,减少了DNA损伤,增加了ATM和CHK2的表达.
与ADAM9表达的干扰增强了思丁的敏感性,增加了DNA损伤 (用γ-H2AX表示),并降低了ATM/CHK2水平.

结论:

在胃癌中,ADAM9在调解青抗性的过程中起着至关重要的作用.
该机制涉及ATM-CHK2DNA损伤修复途径的激活.
在胃癌中,ADAM9是克服化疗耐药性的潜在治疗标.

关键词:

在ADAM9中,ADAM9是ADAM9的前身.在 AGS 找 AGS.西斯普拉丁 (Cisplatin) 是一种修复DNA损伤的修复药物耐药性药物耐药性药物耐药性胃癌是什么?胃癌是什么?

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