通过准其下游信号通路在结肠癌中克服氨酸抗性
Shashank Saurav1, Sourajeet Karfa1, Trung Vu1,2
1Division of Hematology and Oncology, Department of Medicine, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
作为结肠直肠癌 (CRC) 的化疗剂的伊利诺特干,其作用独立于p53. 向OPN和NF-κB通过使癌细胞敏感并克服耐药性来增强氨基酸氨基酸的疗效.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 化疗 化疗是一种化学疗法.
背景情况:
- 伊利诺特坎是转移性结直肠癌 (CRC) 的关键化疗法.
- 目前的免疫疗法只对少量CRCs (微卫星不稳定) 有效.
- 对于开发组合疗法来说,了解氨酸的机制至关重要.
研究的目的:
- 为了研究 irinotekan 对瘤抑制基因和瘤基因的影响.
- 为了确定涉及色素敏感性和耐药性的途径.
- 探索CRC中组合治疗的潜在治疗点.
主要方法:
- 定量实时PCR (qRT-PCR),西式涂抹,免疫光 (IF) 和RNA测序.
- 稳定的敲击,中和抗体,以及对OPN,p53和NF-κB的抑制剂.
- 在体内研究中使用合成基因小鼠模型和全移植瘤.
主要成果:
- 抑制OPN和NF-κB对色素敏感的结肠癌细胞.
- 抑制p53没有影响SN38调节的信号传递,表明p53独立的效应.
- 氨酸抑制了小鼠的瘤生长;RNA-seq显示NF-κB激活调节了免疫/炎症基因,可能导致耐药性.
结论:
- 准OPN,NF-κB,PD-L1和ISG15信号可能会克服CRC中的氨基酸耐药性.
- 伊利诺德坎的疗效部分通过p53独立的途径进行调解.
- 调节免疫和炎症反应可能会增强基于氨基酸的化疗疗效果.
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