RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Fuyuan decoction prevents nasopharyngeal carcinoma metastasis by inhibiting circulating tumor cells/ endothelial cells interplay and enhancing anti-cancer immune response.
Fuyuan decoction prevents nasopharyngeal carcinoma metastasis by inhibiting circulating tumor cells/ endothelial cells interplay and enhancing anti-cancer immune response.
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远处转移是癌症患者治疗失败的主要原因,也是当今改善癌症治疗的关键挑战。我们假设,通过协同多靶点方法增强抗癌免疫反应并抑制循环肿瘤细胞(CTCs)的黏附和跨内皮迁移,可能有效预防癌症转移。“复元汤”(FYD)是一种传统中药复方,广泛用于预防癌症患者术后转移,但其潜在机制仍不清楚。
在本研究中,我们通过体外和体内实验,系统阐明了FYD通过多化合物和多靶点协同作用预防癌症转移的潜在分子机制。FYD在非细胞毒性浓度下通过抑制CTCs与内皮细胞的黏附及其随后的跨内皮迁移,以及增强抗癌免疫反应,显著预防了癌症转移。在机制上,FYD通过调控内皮细胞中NF-κB信号通路抑制TNF-α诱导的CAMs表达,从而阻断CTCs与血管内皮的黏附。FYD通过抑制EMT、PI3K/AKT和FAK信号通路,抑制CTCs的侵袭和迁移。
此外,FYD通过显著增加外周免疫系统中Tc和NK细胞群体,增强抗癌免疫反应。另外,通过UPLC-HRMS测定了FYD的化学成分,结果表明FYD中的多种化合物通过多靶点协同治疗预防癌症转移。
本研究为FYD在预防癌症转移中的应用提供了现代医学依据,并提示多药多靶点协同治疗可能是预防癌症转移的最有效途径之一。
Distant metastasis is a major cause of treatment failure in cancer patients and a key challenge to improving cancer care today.
We hypothesized that enhancing anti-cancer immune response and inhibiting circulating tumor cells (CTCs) adhesion and transendothelial migration through synergistic multi-target approaches may effectively prevent cancer metastasis. "Fuyuan Decoction" (FYD) is a traditional Chinese medicine compound that is widely used to prevent postoperative metastasis in cancer patients, but its underlying mechanism remains unclear.
In this work, we systematically elucidated the underlying molecular mechanism by which FYD prevents cancer metastasis through multi-compound and multi-target synergies in vitro and in vivo . FYD significantly prevented cancer metastasis at non-cytotoxic concentrations by suppressing the adhesion of CTCs to endothelial cells and their subsequent transendothelial migration, as well as enhancing anti-cancer immune response.
Mechanistically, FYD interrupts adhesion of CTCs to vascular endothelium by inhibiting TNF-α-induced CAMs expression via regulation of the NF-κB signaling pathway in endothelial cells. FYD inhibits invasion and migration of CTCs by suppressing EMT, PI3K/AKT and FAK signaling pathways.
Moreover, FYD enhances the anti-cancer immune response by significantly increasing the population of Tc and NK cells in the peripheral immune system.
In addition, the chemical composition of FYD was determined by UPLC-HRMS, and the results indicated that multiple compounds in FYD prevents cancer metastasis through multi-target synergistic treatment.
This study provides a modern medical basis for the application of FYD in the prevention of cancer metastasis, and suggesting that multi-drug and multi-target synergistic therapy may be one of the most effective ways to prevent cancer metastasis.
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