通过高ISG表达介导的瘤中的reovirus耐药性:通过JAK/STAT通路调节克服治疗耐药性
Yuxin Yang1,2, Xiaojin Lin1,3, Liang Chen4
1Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou, China.
Virology journal
|March 6, 2026
概括
抗逆转录病毒治疗的瘤细胞表现出更高的干扰素刺激基因 (ISG) 表达. 抑制JAK-STAT通路可以克服这种抗性,提高菌病毒的疗效.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 雷奥病毒在癌症治疗方面表现有前途,但疗效受到瘤细胞耐药性的限制.
- 了解复原病毒耐药性的分子机制对于改善癌症治疗结果至关重要.
研究的目的:
- 为了研究瘤细胞对reovirus耐药性的分子基础.
- 确定治疗策略,以克服复原病毒耐药性.
主要方法:
- 在12个瘤细胞系中评估了reovirus敏感性.
- 对卵巢癌细胞进行了转录基因分析,这些细胞具有不同的reovirus反应.
- 使用 RO8191 和 ruxolitinib 调节了 JAK-STAT 途径.
- 测试了来自患者的乳腺癌细胞的交叉抗性.
主要成果:
- 根据生存能力,瘤细胞分为敏感,中度和耐药的分层.
- 反复病毒耐药细胞表现出更高的基线干扰素刺激基因 (ISG) 表达,包括干扰素相关的DNA损伤抵抗特征 (IRDS) 基因.
- 抑制JAK-STAT通路减少了ISG,并增强了reovirus的解.
- 升级的ISG和IRDS可能会导致与化疗的交叉耐药性.
结论:
- 升高的基线ISG表达与复原病毒耐药性有关.
- JAK-STAT通路和U-ISGF3可能会调节IRDS上调,从而导致抗性.
- 这些发现为加强对抗性癌症的reovirus治疗提供了基础.
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