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
ACT001 通过上调 NKTR 表达抑制非小细胞肺癌细胞增殖
英文原题：ACT001 inhibits the proliferation of non-small cell lung cancer cells by upregulating NKTR expression.
查看英文原题
ACT001 inhibits the proliferation of non-small cell lung cancer cells by upregulating NKTR expression.
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研究概要
我们的结果表明 NKTR 可能是 ACT001 在 NSCLC 中的靶点。ACT001 有望成为治疗 NSCLC 的一种新方法。
研究思路结论见上方概要
背景
肺癌是全球癌症相关死亡的主要原因，确诊时多处于晚期，预后较差。非小细胞肺癌（NSCLC）是肺部恶性肿瘤的主要组织学类型。本研究探讨了新型倍半萜内酯衍生物ACT001对NSCLC细胞增殖的影响，并探究其潜在机制。
方法
采用克隆形成和MTT实验检测ACT001对细胞增殖的影响。通过RNA-seq分析差异表达基因和富集通路。采用流式细胞术和细胞周期相关蛋白表达分析研究细胞周期。在NKTR KD细胞中，使用AKT激活剂和/或抑制剂检测磷酸化AKT，以探索其机制。在异种移植肿瘤模型中研究ACT001的体内治疗效果。
结果
ACT001抑制了NSCLC细胞系的增殖和G1/S期转换。通过RNA-seq分析，NKTR可能是ACT001的靶点。此外，敲低NKTR促进了细胞增殖并逆转了ACT001的作用。另外，ACT001抑制了AKT磷酸化，但NKTR敲低促进了AKT磷酸化。
展开英文摘要原文
BACKGROUND
Lung cancer, the primary cause of cancer-related deaths worldwide, is diagnosed at an advanced stage and has a poor prognosis. Non-small cell lung cancer (NSCLC) is a major histological type of lung malignancy. This study investigated the effect of ACT001, a novel sesquiterpene lactone derivative, on the proliferation of NSCLC cells and explored the underlying mechanism.
METHODS
The effect of ACT001 on cell proliferation was examined by clone formation and MTT assay. Differentially expressed genes and enrichment pathways were analyzed by RNA-seq. Flow cytometry and cell cycle-related protein expression analysis were performed to study the cell cycle. Phosphorylated AKT was detected to explore the mechanism in natural killer cell triggering receptor (NKTR) KD cells with AKT activator and/or inhibitor. The therapeutic effect of ACT001 in vivo was studied in the xenograft tumor model.
RESULTS
ACT001 inhibited the proliferation and G1/S transition in NSCLC cell lines. By RNA-seq analysis, NKTR may be the target of ACT001. Moreover, knockdown NKTR promoted cell proliferation and reversed the effects of ACT001. In addition, ACT001 inhibited AKT phosphorylation, but NKTR knockdown promoted AKT phosphorylation.
CONCLUSION
Our results suggested NKTR may be the target of ACT001 in NSCLC. ACT001 holds promise as a novel method for the treatment of NSCLC.
论文信息
- 作者
- Zhao M、Qin T、Huang D
- 单位
- Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Thoracic cancer2022 Jun
- 原文标识
- PubMed 35537816 · DOI 10.1111/1759-7714.14453
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