Shen Yili, Cai Haijian, Ma Shenjie, Zhu Wenjing, Zhao Haiyang, Li Jifa, Ye Hua, Yang Lehe, Zhao Chengguang, Huang Xiaoying, Xiao Zhongxiao
Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China.
The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
J Nat Prod. 2022 Apr 22;85(4):765-775. doi: 10.1021/acs.jnatprod.1c00761. Epub 2022 Feb 24.
Non-small-cell lung carcer (NSCLC), the main histological subtype of lung cancer, is responsible for significant morbidity and mortality worldwide. Telocinobufagin, an active compound of the Chinese traditional medicine ChanSu, has antitumor effects, but its mechanism of action remains unknown. Therefore, we investigated the effect of telocinobufagin on NSCLC growth and metastasis and its possible mechanism of action, and . Cell proliferation, migration, and apoptosis were measured by methyl thiazol tetrazolium assay, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, Transwell migration, wound healing, and flow cytometry analysis. A mouse xenograft model was used to evaluate tumor formation . Telocinobufagin was found to suppress proliferation and metastasis and induce apoptosis in human NSCLC cells. Moreover, telocinobufagin was able to significantly inhibit STAT3 phosphorylation at tyrosine 705 (Y) and its downstream targets. Additionally, telocinobufagin also impaired the IL-6-induced nuclear translocation of STAT3. Consistent with the experiments, telocinobufagin reduced the A549 xenograft tumor burden and the levels of P-STAT3, MCL1, BCL2, and cleaved PARP1 . These results support telocinobufagin as a promising STAT3 signaling inhibitor candidate for the treatment of NSCLC patients.
非小细胞肺癌（NSCLC）是肺癌的主要组织学亚型，在全球范围内导致了显著的发病率和死亡率。蟾毒灵是中药蟾酥的一种活性成分，具有抗肿瘤作用，但其作用机制尚不清楚。因此，我们研究了蟾毒灵对NSCLC生长和转移的影响及其可能的作用机制。通过甲基噻唑四唑盐法、集落形成、5-乙炔基-2'-脱氧尿苷掺入、Transwell迁移、伤口愈合和流式细胞术分析来检测细胞增殖、迁移和凋亡。使用小鼠异种移植模型来评估肿瘤形成。发现蟾毒灵可抑制人NSCLC细胞的增殖和转移并诱导其凋亡。此外，蟾毒灵能够显著抑制STAT3在酪氨酸705（Y）位点的磷酸化及其下游靶点。另外，蟾毒灵还损害了IL-6诱导的STAT3核转位。与体外实验一致，蟾毒灵降低了A549异种移植瘤的负担以及P-STAT3、MCL1、BCL2和裂解的PARP1的水平。这些结果支持蟾毒灵作为治疗NSCLC患者的一种有前景的STAT3信号抑制剂候选药物。
