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
减毒鼠伤寒沙门菌递送 STAT3-siRNA 与内皮抑素共表达质粒用于结直肠癌的免疫与血管生成调控
英文原题：Attenuated S. typhimurium delivery of STAT3-siRNA and endostatin co-expression plasmids for immune and angiogenesis modulation in colorectal cancer.
查看英文原题
Attenuated S. typhimurium delivery of STAT3-siRNA and endostatin co-expression plasmids for immune and angiogenesis modulation in colorectal cancer.
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研究概要
本研究中使用的联合基因治疗对结直肠同种移植瘤生长具有叠加抑制作用。
研究思路结论见上方概要
背景
结直肠癌（CRC）是全球男性第三大常见癌症，女性第二大常见癌症。由于其高转移率和不良预后，CRC 是全球癌症相关死亡的主要原因。
方法
联合基因治疗是一种有前景的治疗方法，可用于改变与癌症发生和发展相关的基因。本报告描述了使用一种真核共表达质粒，该质粒同时编码STAT3 siRNA（si-STAT3）和内皮抑素，用于治疗C57BL/6小鼠的CRC同种移植瘤，并利用减毒鼠伤寒沙门氏菌（S. typhimurium）促进质粒的高效递送。
结果
在本研究中，单独使用si-STAT3或endostatin治疗在CRC同种移植模型中均显示出抗肿瘤效果，而共表达治疗具有更显著的抗肿瘤效果。共表达质粒不仅改变了STAT3和endostatin的表达，该治疗还下调了MMP2和cyclin D1的表达，并上调了caspase 3的表达。CD4 + T细胞、CD8 + T细胞、NK细胞和CD4 + CD25 + Foxp3 + 调节性T细胞（Treg细胞）的水平也受到联合治疗的影响。此外，联合治疗改变了细胞因子的表达，增强了抗肿瘤免疫。
展开英文摘要原文
BACKGROUND
Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. Due to its high metastasis rate and poor prognosis, CRC is the leading cause of cancer-related deaths worldwide.
MATERIALS AND METHODS
Combined gene therapy is a promising treatment that can be used to alter the genes involved in cancer genesis and development. This report describes the use of a eukaryotic co-expression plasmid that encodes both STAT3 siRNAs (si-STAT3) and endostatin for the treatment of CRC homografts in C57BL/6 mice, with attenuated Salmonella typhimurium (S. typhimurium) used to facilitate efficient delivery of the plasmid.
RESULTS
In this study, single treatment with either si-STAT3 or endostatin showed antitumor effects in the CRC homograft model, and the co-expression treatment had more significant antitumor effects. Not only did the co-expressed plasmids alter the STAT3 and endostatin expression, this treatment also down-regulated MMP2 and cyclin D1 expression and up-regulated caspase 3 expression. The levels of CD4 + T cells, CD8 + T cells, NK cells, and CD4 + CD25 + Foxp3 + regulatory T cells (Treg cells) were also affected by the combined treatment. In addition, the combined therapy altered cytokine expression, enhancing antitumor immunity.
CONCLUSION
The combined gene therapy used in this study additively inhibited colorectal homograft tumor growth.
论文信息
- 作者
- Cui A、Fan W、Huang T、Li X、Xiong W、Wang Y、Chen Y
- 第一作者单位
- Department of Clinical Laboratory, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.China
- 通讯作者单位
- Department of Clinical Laboratory, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China. Electronic address: cy4402@stu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Immunobiology2025 Nov
- 原文标识
- PubMed 41429696 · DOI 10.1016/j.imbio.2025.153129