Wan Min, Yu Hong, Zhai Haoqing
Department of Medical Laboratory, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, 430014, China.
Department of Oncology Hematology, Qianjiang Central Hospital, No.22 Zhanghua Road, Qianjiang, 433100, Hubei, China.
Mol Biotechnol. 2025 Apr;67(4):1526-1538. doi: 10.1007/s12033-024-01136-3. Epub 2024 Apr 2.
It has bene reported that a novel saponin-notoginsenoside R1 (NGR1) possesses strong anti-tumor activities. This study aimed to investigate the role and mechanism of NGR1 in non-small cell lung cancer (NSCLC). NSCLC cell viability, proliferation, migration, and invasiveness were assessed using the ex vivo assays. NSCLC xenograft mouse models were constructed to confirm the role of NGR1 in vivo. Epithelial-mesenchymal transition (EMT)-related proteins and key markers in the JAK2/STAT3 pathway were examined using immunoblotting and immunohistochemistry analyses. NGR1 treatment suppressed NSCLC cell growth ex vivo and in vivo. It also decreased the migratory and invasive capacities of NSCLC cells. Additionally, NGR1 increased E-cadherin expression and reduced N-cadherin, vimentin, and snail expression in TGF-β1-treated NSCLC cells and xenograft tumors. JAK2/STAT3 pathway was inhibited by NGR1. Moreover, a specific inhibitor of JAK2, AG490, or STAT3 silencing significantly enhanced the effects of NGR1 against the EMT process in NSCLC cells. NGR1 restrains EMT process in NSCLC by inactivating JAK2/STAT3 signaling, suggesting the potential of NGR1 in anti-NSCLC therapy.
据报道，一种新型皂苷——三七皂苷R1（NGR1）具有强大的抗肿瘤活性。本研究旨在探讨NGR1在非小细胞肺癌（NSCLC）中的作用及机制。使用体外实验评估NSCLC细胞的活力、增殖、迁移和侵袭能力。构建NSCLC异种移植小鼠模型以证实NGR1在体内的作用。使用免疫印迹和免疫组织化学分析检测上皮-间质转化（EMT）相关蛋白和JAK2/STAT3通路中的关键标志物。NGR1处理在体外和体内均抑制NSCLC细胞生长。它还降低了NSCLC细胞的迁移和侵袭能力。此外，NGR1增加了TGF-β1处理的NSCLC细胞和异种移植肿瘤中E-钙黏蛋白的表达，并降低了N-钙黏蛋白、波形蛋白和蜗牛蛋白的表达。NGR1抑制JAK2/STAT3通路。此外，JAK2的特异性抑制剂AG490或STAT3沉默显著增强了NGR1对NSCLC细胞EMT过程的作用。NGR1通过使JAK2/STAT3信号失活来抑制NSCLC中的EMT过程，提示NGR1在抗NSCLC治疗中的潜力。
