基因改造的沙门氏菌,SGN1,作为一种瘤微环境向模式,能够降低口腔状细胞癌的 metionin
Ping Mao1, Xiangqian Wang2, Yuerong Peng3
1The International Translational Medical Research Center, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, China; College of Traditional Chinese Medicine, Bozhou University, Anhui, Bozhou, China.
概括
口腔状细胞癌 (OSCC) 细胞表现出异常的氨酸代谢,推动瘤生长. 一种新型的沙门氏菌typhimurium菌株 (SGN1) 有效地消耗瘤氨酸,以最小的毒性抑制OSCC的进展.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 微生物学 微生物学
背景情况:
- 代谢重编程是癌症的一个关键标志.
- 准氨基酸代谢是一个有前途的治疗策略.
- 氨酸代谢异常与口腔状细胞癌 (OSCC) 的预后不佳有关.
研究的目的:
- 调查甲胺代谢在OSCC中的作用.
- 开发和评估OSCC针对 metionin代谢的新型治疗方法.
主要方法:
- 临床OSCC样本的生物信息分析.
- 使用培养OSCC细胞进行体外研究.
- 使用OSCC异种移植模型的体内研究 (皮下和正体).
- 开发和应用SGN1,一种过度表达L-甲氨酶 (METase) 的工程Salmonella typhimurium菌株.
- 在患者衍生器官 (PDO) 中评估SGN1的疗效和安全性,并通过血液学,生化学和遗传病学分析.
主要成果:
- 在OSCC临床样本中发现了 metionin代谢异常,与预后不佳相关.
- 甲因缺乏抑制了OSCC细胞的增殖和迁移在体外.
- 饮食中氨酸的限制抑制了瘤的生长,但导致了全身毒性.
- SGN1选择性地殖民瘤,降低了内甲氨酸水平,并在 ортотоп模型中显示出卓越的抗瘤疗效.
- SGN1 显示了持续的瘤定居,并抑制了 PDO 的扩散,具有有利的安全性.
结论:
- 氨酸依赖是人类OSCC的一个关键漏洞.
- SGN1代表了一种耐受良好,瘤微环境向的氨酸消耗疗法,在OSCC治疗中具有显著的翻译潜力.
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