期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 13, 期 -, 页码 3539-3550出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S216542
关键词
indole analog; triple-negative breast cancer; cell cycle arrest; apoptosis; Akt; mTOR
资金
- Natural Science Foundation of Zhejiang Province [LY17B020008, LR18H160003, LYI6H160050]
- National Natural Science Foundation of China [81750110549, 81622043]
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer which is associated with poor patient outcome and lack of targeted therapy. Our laboratory has synthesized a series of indole-2-carboxamide derivatives. Among this series, compound LG25 showed a favorable pharmacological profile against sepsis and inflammatory diseases. In the present study, we investigated the chemotherapeutic potential of LG25 against TNBC utilizing in vitro and in vivo models. Methods: Changes in cell viability, cell cycle phases and apoptosis were analyzed using MTT, clonogenic assay, FACS and Western blotting assays. The anti-cancer effects of LG25 were further determined in a xenograft mouse model. Results: Our findings reveal that LG25 reduced TNBC viability in a dose-dependent manner. Flow cytometric and Western blot analyses showed that LG25 enhances G2/M cell cycle arrest and induced cell apoptosis. In addition, LG25 treatment significantly inhibited Akt/mTOR phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-kappa B). These inhibitory activities of LG25 were confirmed in mice implanted MDA-MB-231 TNBC cells. Conclusion: Our studies provide experimental evidence that indole-2-carboxamide derivative LG25 effectively targeted TNBC in preclinical models by inducing cell cycle arrest and apoptosis, through suppressing Akt/mTOR/NF-kappa B signaling pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据