瘤细胞的适应性变化,以应对减弱性压力
Leilei Zhang1, Jie Zhang1, Zhi-Wei Ye1
1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA.
Biochemical pharmacology
|November 24, 2023
概括
瘤细胞可以适应致命的还原性压力,这种情况与癌症有关. 发展抗药性会改变细胞分裂,新陈代谢和线粒体功能,增强生存机制.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 生物化学 生物化学
背景情况:
- 减少性压力,细胞电子捐赠者的不平衡,与癌症等人类病理有关.
- 黑色素瘤细胞系被设计为对减轻性压力剂的耐药性:轮 (ROT),n-乙-L-氨酸 (NAC) 和dithiothreitol (DTT).
研究的目的:
- 研究黑色素瘤细胞中细胞适应和代谢变化的研究,研究黑色素瘤细胞对减少性压力产生抵抗力.
- 了解减少性应激抵抗对细胞形态,线粒体功能和关键信号通路的影响.
主要方法:
- 发展出抗性黑色素瘤细胞系 (ROT,NAC,DTT).
- 分析细胞形态,线粒体形态,膜潜力和呼吸.
- 评估细胞代谢流量,包括利用三碳酸 (TCA) 循环中间体和体.
- 测量反应性氧物种 (ROS) 水平,核因素红色素2相关因子2 (Nrf2) 激活,以及未折叠的蛋白质反应 (UPR) 表达.
主要成果:
- 耐药细胞表现出更快的分裂和更低的细胞内氧化还原状态.
- ROTR细胞显示出显著的线粒体变化 (碎片化,胀,脱极化) 和减少呼吸.
- NACR和DTTR细胞使用TCA循环中间体,而ROTR细胞使用体.
- 电阻与ROS降低,Nrf2/GSTP通路激活和UPR信号增加相关.
结论:
- 黑色素瘤细胞通过改变新陈代谢和增强生存途径来适应致命的减少压力.
- 降低性抗压力会诱导不同的线粒体和代谢特征,共同趋势是增加UPR.
- 这些发现突显了瘤细胞适应敌对减少环境的适应性,这对于了解癌症进展和治疗耐药性至关重要.
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