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蛋白质酶抑制剂可以通过减少NSCLC细胞中的p-ERK来部分降低CD73的表达

Ai-Ling Su¹, Chang-Qing Tian¹, Ying-Jie Ou¹

¹State Key Laboratory of Drug Research, Cancer Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

|September 28, 2023

概括

蛋白质酶抑制剂通过影响MAPK通路来降低CD73,一种与瘤免疫抑制相关的蛋白质. 过度表达CD73会降低蛋白酶体抑制剂的有效性,从而揭示出新的抗癌机制.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

埃克托-5'-核酶 (CD73) 促进瘤免疫抑制,是抗癌药物开发的目标.
蛋白酶体抑制剂是临床上使用的癌症治疗药物,这些药物会损害蛋白质降解.

研究的目的:

为了研究蛋白酶体抑制剂对非小细胞肺癌 (NSCLC) 中的CD73表达的影响.
阐明MAPK途径在调节蛋白酶体抑制剂对CD73的调节中的作用.
评估CD73过度表达对蛋白酶体抑制剂体内疗效的影响.

主要方法:

用蛋白酶体抑制剂和小分子药物治疗NSCLC细胞系 (NCI-H1299,其他).
分析CD73,ERK和p-ERK蛋白质和mRNA水平,使用西方涂抹和RT-qPCR.
使用MEK和ERK抑制剂和纤维细胞生长因子2 (FGF2) 调查MAPK通路.
在实验室和体内对小鼠易斯肺癌 (LLC) 细胞的CD73过度表达效应的评估,包括Bortezomib治疗.

主要成果:

蛋白质酶抑制剂始终降低了NSCLC细胞中CD73的蛋白质和mRNA水平.
涉及ERK和p-ERK的MAPK途径也与此有关,因为MEK和ERK抑制剂也降低了CD73水平.
FGF2治疗部分挽救了CD73的减少,这表明途径参与.
过度表达CD73在体外没有影响蛋白酶体抑制剂的有效性,但显著降低了Bortezomib在体内抗癌活性.

结论:

蛋白质酶抑制剂降低CD73表达,可能通过调节MAPK通路.
CD73在蛋白酶体抑制剂的体内疗效方面发挥着关键作用,特别是博特佐米布.
这些发现为蛋白酶体抑制剂的抗癌机制提供了新的见解,并强调CD73是影响治疗反应的潜在因素.

关键词:

CD73 CD73 CD73 CD73 CD73 CD73 CD73 CD73 CD73 CD73 CD73 埃尔克·埃尔克是什么意思在NSCLCLC中,我们可以看到.蛋白质酶体抑制剂蛋白质酶体抑制剂

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