从肺癌细胞中分泌的免疫调节性高流动性群体第1框 (HMGB1) 蛋白质的西斯胺依赖分泌

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Kevin P Gillespie¹, Ross Pirnie¹, Clementina Mesaros¹

¹Center of Excellence in Environmental Toxicology, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Biomolecules

|September 28, 2023

概括

西斯丁,但不是碳丁,通过核出口素1 (XPO1) 在肺癌细胞中触发高流动性组盒1 (HMGB1) 的分泌. 降低HMGB1可能会提高免疫疗法的疗效.

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:

高流动性组盒1 (HMGB1) 是各种细胞分泌的蛋白质,影响免疫反应和癌症.
转化后的修饰,如乙化和氧化,会影响HMGB1的细胞外功能.
HMGB1在癌症的进展和免疫调节中起作用.

研究的目的:

研究思丁和碳丁对非小细胞肺癌 (NSCLC) 细胞中HMGB1分泌的影响.
为了确定青诱导的HMGB1分泌的调节机制.
探索HMGB1调制在NSCLC中的潜在治疗影响.

主要方法:

使用了人类A549NSCLC细胞.
给药的西斯和卡博普拉丁化疗剂.
采用免疫沉,稳定同位素稀释,差异化和纳米LC-PRM/HRMS测定.
监测HMGB1水平,乙化和氧化状态.

主要成果:

与卡博普拉丁不同的是,西斯普拉丁诱导了A549 NSCLC细胞的剂量依赖HMGB1分泌.
西斯丁介导的HMGB1分泌是由核出口蛋白1 (XPO1) 调节的,而不是ADP-ribosylation,乙化或氧化.
低剂量西斯丁治疗导致HMGB1分泌减少,而DMSO诱导的亡导致氧化HMGB1.
发现分泌的HMGB1在低剂量西斯治疗后主要以减少的形式存在.

结论:

抑制XPO1可以通过增加核HMGB1来增强西斯的抗瘤作用,这抑制了DNA补充物修复.
低剂量西斯可能通过减少细胞外HMGB1的化学激素活性来调节NSCLC中的免疫反应.
这种免疫调节可能会提高后续免疫治疗的有效性.

关键词:

通过乙化处理.染色体学染色体学染色体学免疫反应的免疫反应.质谱测量质谱测量质谱测量质量测量质谱测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量质量测量氧化过程中的氧化.类药物是一种类药物.

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