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.
Thorac Cancer. 2022 Jun;13(12):1772-1782. doi: 10.1111/1759-7714.14453. Epub 2022 May 10.
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.
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.
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.
Our results suggested NKTR may be the target of ACT001 in NSCLC. ACT001 holds promise as a novel method for the treatment of NSCLC.
肺癌是全球癌症相关死亡的主要原因，通常在晚期诊断，预后较差。非小细胞肺癌（NSCLC）是一种主要的肺癌组织学类型。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，并探讨了其潜在机制。
通过集落形成和 MTT 检测评估 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。通过流式细胞术和细胞周期相关蛋白表达分析研究细胞周期。通过天然杀伤细胞触发受体（NKTR）KD 细胞的 AKT 激活剂和/或抑制剂检测磷酸化 AKT 以探索机制。在异种移植肿瘤模型中研究 ACT001 的体内治疗效果。
ACT001 抑制 NSCLC 细胞系的增殖和 G1/S 期过渡。通过 RNA-seq 分析，NKTR 可能是 ACT001 的靶点。此外，NKTR 敲低促进细胞增殖并逆转了 ACT001 的作用。此外，ACT001 抑制 AKT 磷酸化，但 NKTR 敲低促进 AKT 磷酸化。
我们的研究结果表明，NKTR 可能是 NSCLC 中 ACT001 的靶点。ACT001 有望成为治疗 NSCLC 的新方法。
