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氨酸通过PI3K/Akt/mTOR通路调节巨细胞极化和功能来抑制瘤生长
Hyeonha Jang1,2, Uttam Ojha1,2, Ji-Hak Jeong1,2
1Vessel-Organ Interaction Research Center (VOICE, MRC), College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea.
Archives of pharmacal research
|July 19, 2023
概括
素是一种天然化合物,通过抑制M2型瘤相关巨细胞 (TAMs) 和通过PI3K/Akt/mTOR途径重塑瘤微环境 (TME) 来抑制瘤生长.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 瘤微环境 (TME) 中的瘤相关巨细胞 (TAM) 促进瘤进展,血管生成,转移和治疗抵抗.
- 肌素是一种天然化合物,具有免疫抑制和抗瘤特性,但其对TAM的影响尚不清楚.
研究的目的:
- 为了研究髓素对TAMs和TAM介导的瘤生长的影响.
- 在体外和体内阐明髓素对TAMs作用的潜在机制.
主要方法:
- 评估了氨酸对单细胞-巨细胞分化和两极化 (M1/M2) 的影响.
- 分析了M2巨细胞中的细胞因子表达,益血管性因子分泌和内皮细胞透性.
- 研究了M2巨细胞中的PI3K/Akt/mTOR信号通路.
- 评估了myriocin对TAM群体在小鼠全移植瘤模型中的影响.
- 检查了myriocin和cisplatin对瘤生长和存活的协同作用.
主要成果:
- 氨酸抑制了单细胞-巨细胞分化和M2极化,但没有抑制M1极化.
- 髓素抑制了与巨细胞相关的M2抗炎细胞因子和益血管原因子 (例如,VEGF).
- 氨酸在体内减少了类似M2的TAM,并抑制了M2巨细胞中的PI3K/Akt/mTOR通路.
- 结合米里奥辛和西斯普拉丁治疗协同抑制了瘤生长,并通过减少M2类TAMs来改善存活率.
结论:
- 髓素通过抑制M2类TAM分化和两极化来抑制瘤生长.
- PI3K/Akt/mTOR信号通路是myriocin抗TAM作用的关键目标.
- 髓素显示出作为重塑TME和增强抗癌疗法的治疗剂的潜力.
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