抑制PGC1α通过重编程能量代谢来抑制失塑性口腔角质细胞的增殖
Yunkun Liu1, Nengwen Huang1, Xianghe Qiao1
1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
降低PGC1α (氧酶增殖器激活受体-型协作激活剂-1α) 通过改变细胞能量代谢来抑制口腔潜在恶性疾病 (OPMD) 细胞生长和瘤进展. 这突出了PGC1α作为OPMD的潜在治疗点.
科学领域:
- 在瘤学瘤学.
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- 口腔潜在恶性疾病 (OPMDs) 可以发展为口腔状细胞癌 (OSCC).
- 细胞能量代谢的改变是癌症的标志,PGC1α (氧酶增殖器激活受体-马联合激活器-1α) 对线粒体功能至关重要.
- PGC1α在OPMD进展中的确切作用尚不清楚.
研究的目的:
- 调查PGC1α对人类异形性口腔角质细胞 (DOKs) 的全面影响.
- 阐明PGC1α影响OPMD进展和细胞能量代谢的分子机制.
- 评估PGC1α作为OPMD的潜在治疗点.
主要方法:
- 在DOK中抑制PGC1α,并在体外评估细胞增殖,细胞循环和细胞亡.
- 在体内进行异种移植瘤研究,以评估瘤生长.
- 分析线粒体DNA (mtDNA),电子运输链 (ETC) 复合体,活性氧物种 (ROS),氧消耗率 (OCR),细胞外酸化率 (ECAR) 和葡萄糖吸收.
- 用SR18292治疗,它是一种PGC1α的抑制剂.
主要成果:
- 抑制PGC1α显著抑制DOK增殖和瘤生长,诱导S相停止并抑制PI3K/Akt通路而不会影响亡.
- 下调PGC1α降低了mtDNA,ETC和OCR,同时通过乳酸脱酶A (LDHA) 调节增加了ROS,葡萄糖吸收,ECAR和糖解.
- 治疗SR18292诱导了氧化酸化功能障碍,并减少了DOK异种移植瘤的进展.
结论:
- 通过重编程细胞能量代谢,PGC1α在OPMD细胞增殖中发挥着关键作用.
- 与PGC1α介导的能量代谢的干扰为OPMDs提供了潜在的治疗策略.
- 向PGC1α可能为OPMD治疗提供一种新的方法.
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