白藜芦醇、姜黄素和槲皮素复合物对乳腺肿瘤小鼠免疫抑制的影响。
The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice.
发表日期:2023 Aug 16
作者:
Chenchen Li, Yajun Xu, Junfeng Zhang, Yuxi Zhang, Wen He, Jiale Ju, Yinghua Wu, Yanli Wang
来源:
TROPICAL MEDICINE & INTERNATIONAL HEALTH
摘要:
白藜芦醇、姜黄素和槲皮素是药食同源植物的次生代谢产物,已被证明在癌症治疗中具有潜在作用。然而,单一成分的抗肿瘤效果较弱。因此,本研究设计了一种名为RCQ的抗肿瘤化合物,由白藜芦醇、姜黄素和槲皮素组成。本研究检查了通过胃内给予RCQ对4T1乳腺癌携带小鼠的肿瘤发生和发展的影响。RCQ增加了T细胞的招募,减少了肿瘤微环境中中性粒细胞和巨噬细胞的积累。同时,RCQ抑制了肿瘤浸润淋巴细胞向免疫抑制细胞亚群的发展,包括CD4+T细胞向T辅助2型细胞(Th2)、肿瘤相关中性粒细胞(TANs)到N2 TANs和肿瘤相关巨噬细胞(TAMs)细胞到M2 TAMs。RCQ逆转了肿瘤微环境中免疫抑制性浸润细胞的优势地位,将免疫平衡倾向于免疫激活状态。体外研究表明,RCQ显著增加了肿瘤细胞中的活性氧(ROS),降低了线粒体膜电位,并调节了促凋亡的Bcl-2家族成员。总之,RCQ能促进肿瘤细胞的ROS凋亡机制,并缓解肿瘤微环境的免疫抑制作用,增强抗肿瘤效果。©2023 Springer Nature Limited.
Resveratrol, curcumin, and quercetin are the secondary metabolites from medicinal food homology plants, that have been proven their potency in cancer treatment. However, the antitumor effect of a single component is weak. So, herein, we designed an antitumor compound named RCQ composed of resveratrol, curcumin, and quercetin. This study examined the effect on tumorigenesis and development of 4T1 breast cancer-bearing mice following administering RCQ by intragastric administration. RCQ increased the recruitment of T cells and reduced the accumulation of neutrophils and macrophages in the tumor microenvironment. Meanwhile, RCQ suppressed the development of tumor-infiltrating lymphocytes into immunosuppressive cell subpopulations, including CD4+ T cells to T helper Type 2 type (Th2), tumor-associated neutrophils (TANs) to the N2 TANs, and tumor-associated macrophages (TAMs) cells to M2 TAMs. RCQ reversed the predominance of immunosuppressive infiltrating cells in the tumor microenvironment and tipped the immune balance toward an immune activation state. In vitro the study showed that RCQ significantly increased reactive oxygen species (ROS), reduce mitochondrial membrane potentials in cancer cells, and modulate pro-apoptotic Bcl-2 family members. In conclusion, RCQ can promote the ROS apoptosis mechanism of tumor cells and alleviate immunosuppression of the tumor microenvironment to enhance the anti-tumor effect.© 2023. Springer Nature Limited.