THOC2表达及其对多形质母细胞瘤中5-甲抗性的影响
Young Jun Lee1,2, Jin-Hwa Jung1,3, Da-Young Chang1,3
1Department of Anatomy, Ajou University School of Medicine Suwon, South Korea.
American journal of cancer research
|July 10, 2023
概括
在多种质母细胞瘤 (GBM) 中,THOC2表达与5-甲 (5-FU) 耐药性显著相关. 准THOC2可能会提高5FU治疗对GBM患者的有效性.
科学领域:
- 神经瘤学神经瘤学
- 癌症生物学 癌症生物学
- 分子治疗学分子治疗学
背景情况:
- 多形质母细胞瘤 (GBM) 是一种具有有限治疗选择的侵袭性脑瘤.
- 5-甲 (5-FU) 在GBM治疗中显示出潜力,特别是在先进的药物输送中.
- 了解耐药机制对于提高GBM治疗疗效至关重要.
研究的目的:
- 调查THOC2表达在GBM中的5-FU耐药性中的作用.
- 评估THOC2水平与对5-FU敏感度之间的相关性.
- 探索THOC2作为克服5-FU抗性的潜在治疗标.
主要方法:
- 在GBM细胞系和初级质瘤细胞中评估了5-FU敏感性,细胞翻倍时间和基因表达.
- 通过长期暴露于5-FU,开发出耐5FU的GBM细胞系 (例如T98FR).
- 在试验室和老鼠异种移植模型中利用THOC2敲除,随后进行RNA测序.
主要成果:
- 在GBM细胞中,高THOC2表达和5-FU抗性之间观察到显著的相关性.
- 在5-FU耐药细胞中,THOC2表达被上调,而THOC2倒置降低了5-FU IC50值.
- 在活体中,THOC2敲击减弱了瘤生长,并改善了5 - FU治疗小鼠的存活率.
- 在THOC2 Knockdown中,改变了Bcl-x拼接 (增加了亲细胞灭绝的Bcl-xS),并减少了L1CAM表达,影响了细胞粘附和迁移.
结论:
- 在质母细胞瘤中,THOC2在调解5-FU耐药性方面发挥着至关重要的作用.
- 准THOC2是一个有希望的策略,可以提高基于5-FU的治疗方法对GBM的疗效.
- 对THOC2调节的进一步研究可能会为GBM患者改善治疗结果.
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