维素通过通过EGFR信号调节巨细胞极化来抑制TNBC进展和转移
Yufeng Lin1, Lin Li1, Huakang Huang1
1Department of Breast Care Surgery, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, PR China.
Journal of immunotherapy (Hagerstown, Md. : 1997)
|June 7, 2024
概括
维素通过抑制瘤生长和侵袭来对抗三阴性乳腺癌 (TNBC). 它还将与瘤相关的巨细胞 (TAM) 重编程为抗癌M1状态,提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 三阴性乳腺癌 (TNBC) 由于其侵略性和缺乏向治疗方法,因此存在重大治疗挑战.
- 瘤相关巨细胞 (TAMs) 是TNBC进展的关键参与者,通常采用一种亲瘤起源的M2表型.
- 天然化合物维捷辛对TNBC中TAM的治疗潜力在很大程度上仍未得到研究.
研究的目的:
- 为了研究维捷辛对TNBC细胞的抗癌作用.
- 确定维捷辛在瘤微环境中调节巨细胞两极分化 (M1与M2) 的作用.
- 为了阐明EGFR/PI3K/AKT/mTOR信号通路在维捷辛的作用机制中的参与.
主要方法:
- 在体外评估维捷辛对TNBC细胞增殖和侵入的影响 (MDA-MB-231,BT549).
- 在维捷克辛治疗后分析巨细胞极化标记物和细胞因子概况.
- 对EGFR酸化和下游信号通路激活的评估 (PI3K/AKT/mTOR).
- 使用TNBC异种移植模型进行体内研究,以评估瘤生长抑制和TAM两极分化.
主要成果:
- 维素显著抑制了TNBC细胞的增殖和侵入.
- 维素治疗促进了M1巨细胞的两极分化,并抑制了M2的两极分化,同时还诱导了巨细胞衍生的抗癌媒介.
- 维素调节了EGFR/PI3K/AKT/mTOR通路,减少了EGFR的酸化.
- 在体内,维捷辛抑制了瘤生长,并将TAM转移到M1表型,证明了与多克索鲁比辛的协同作用.
结论:
- 维素通过直接抑制癌细胞和重编程瘤微环境,对TNBC表现出强大的抗癌特性.
- 维素能够促进M1巨分化并抑制M2分化,这为TNBC提供了一种新的免疫调节治疗策略.
- 向EGFR/PI3K/AKT/mTOR通路是维特辛在TNBC中有效性的关键机制,表明其作为治疗剂的潜力,可能在组合治疗中.
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