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:Deziyangxin suppresses non-small cell lung cancer through remodeling of the tumor immune microenvironment.
Deziyangxin suppresses non-small cell lung cancer through remodeling of the tumor immune microenvironment.
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DZYX 在 NSCLC 中发挥抗肿瘤活性,与肿瘤免疫微环境重塑及多通路分子调控相关。这些发现为 DZYX 在肿瘤相关疾病中的传统应用提供了机制支持,并凸显其作为肺癌治疗免疫调节候选药物的潜力。
本研究旨在评估DZYX在非小细胞肺癌(NSCLC)中的抗肿瘤疗效,并探讨其潜在机制,重点关注肿瘤免疫微环境调控。
采用LC-MS/MS进行血清药物化学分析,以鉴定DZYX的循环成分。建立同基因Lewis肺癌(LLC)小鼠模型,以78.5 mg/kg或157 mg/kg的剂量通过灌胃给予DZYX治疗25天。评估肿瘤生长和组织病理学,同时采用转录组学分析、网络药理学、流式细胞术和免疫组织化学研究分子通路和免疫细胞浸润。
LC-MS/MS 鉴定出 167 种来源于 DZYX 的循环成分。DZYX 治疗显著抑制了 LLC 荷瘤小鼠的肿瘤生长并诱导肿瘤坏死。转录组学和富集分析表明其调节了趋化因子信号通路、T 细胞活化和先天免疫通路。流式细胞术和免疫组织化学进一步证明肿瘤组织和脾脏内 CD4 + 和 CD8 + T 细胞、NK 细胞和 B 细胞的浸润增加。肿瘤内 Granzyme B 和 IFN-γ 信号增强,提示细胞毒性免疫活性增加。
Serum pharmacochemistry was performed using LC-MS/MS to identify circulating constituents of DZYX. A syngeneic Lewis lung carcinoma (LLC) mouse model was established in mice, which were treated with DZYX by oral gavage at 78.5 mg/kg or 157 mg/kg for 25 days. Tumor growth and histopathology were evaluated, while transcriptomic analysis, network pharmacology, flow cytometry, and immunohistochemistry were used to investigate molecular pathways and immune cell infiltration.
LC-MS/MS identified 167 circulating components derived from DZYX. DZYX treatment significantly suppressed tumor growth and induced tumor necrosis in LLC-bearing mice. Transcriptomic and enrichment analyses indicated modulation of chemokine signaling, T-cell activation, and innate immune pathways. Flow cytometry and immunohistochemistry further demonstrated increased infiltration of CD4 + and CD8 + T cells, NK cells, and B cells within tumor tissues and spleens. Enhanced intratumoral Granzyme B and IFN-γ signals suggested increased cytotoxic immune activity.
DZYX exerts anti-tumor activity in NSCLC associated with remodeling of the tumor immune microenvironment and multi-pathway molecular regulation. These findings provide mechanistic support for the traditional use of DZYX in tumor-related disorders and highlight its potential as an immunomodulatory candidate for lung cancer therapy.
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