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与M2瘤相关的巨细胞通过加强EZH2促进了肺癌转移中的DNA甲基化
Zheming Li1, Jing Luo2, Kaixiang Zhao2
1College of Pharmacy, Zhejiang Chinese Medical University.
Anti-cancer drugs
|August 24, 2023
概括
与瘤相关的巨细胞 (TAMs) 通过增强EZH2表达和DNA甲基化来促进肺癌的进展. 抑制EZH2有效降低瘤生长和转移,提供一种潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 在肺癌微环境中,瘤相关巨细胞 (TAMs) 与增强性胃同源2 (EZH2) 之间的相互作用尚未得到充分理解.
- 由IL-4和IL-13诱导的M2型TAM在瘤进展中起着重要作用.
研究的目的:
- 为了研究TAMs和EZH2在肺癌中的相互作用.
- 评估M2 TAMs对肺癌细胞增殖,迁移和入侵的影响.
- 探索针对肺癌中EZH2的治疗潜力.
主要方法:
- 在RAW264.7细胞中使用IL-4和IL-13诱导M2TAMs.
- 在体外与LCL-1肺癌细胞共同培养M2 TAMs.
- 在体内研究涉及向LCL-1细胞携带小鼠注射M2 TAM.
- 对DNA甲基化,EZH2表达和基因调节的评估.
- 使用GSK126对EZH2进行药理抑制,使用si-EZH2.2进行遗传抑制.
主要成果:
- M2 TAM共同培养增强了LCL-1细胞的增殖,迁移,入侵,瘤生长和转移.
- M2 TAMs增加了DNA甲基化和EZH2水平,同时降低了EZH2基因 (p21,CDKN2A,CDKN2B).
- EZH2抑制 (GSK126,si-EZH2) 逆转了M2 TAM诱导的影响,抑制了LCL-1细胞转移和瘤生长.
结论:
- M2 TAMs通过EZH2-介导的DNA甲基化促进肺癌的进展.
- 向EZH2代表了肺癌的有希望的治疗策略,特别是在TAM透的背景下.
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