乳腺癌
PI3K/AKT/mTOR通路
自噬
癌症研究
转移
蛋白激酶B
转移性乳腺癌
癌症
下调和上调
细胞凋亡
体内
医学
癌细胞
化学
生物
内科学
生物化学
生物技术
基因
作者
Zhen Gao,Yan Zhang,Weixing Shen,Xinyu Liu,Yunfang Wei,Lin-xia Li,Hengguan Cui
摘要
Abstract Although there have been significant advances in cancer treatment, the urgent need to inhibit breast cancer metastasis remained unmet. Bruceine A (BA) is a natural compound extracted from Bruceae Fructus and has long been recognized to have antitumor effects with high safety and biocompatibility. However, the mechanisms and/or targets of BA for metastatic breast cancer treatment are still not fully elucidated. In this study, we systematically investigated the effects of BA on inhibition of breast cancer metastasis and its underlying mechanisms. We found that, in addition to its cytotoxic effects, BA significantly inhibited the invasion and migration capabilities of two types of breast cancer cell lines (MDA‐MB‐231 and MCF‐7) while concurrently promoting apoptosis in these cells. Further mechanistic studies revealed that, by targeting the canonical PI3K‐AKT signaling pathway, BA initiated autophagy of both types of breast cancer cell lines in vitro. In vivo results further confirmed the in vitro findings, manifested by shrinkage of size and weight of breast tumor as well as initiation of autophagy (indicated by upregulation of LC3I/II) through targeting PI3K‐AKT pathway on mice model. These data collectively demonstrated the potential of BA in antimetastasis of breast cancer cells, suggesting its future clinical transformation in metastatic breast cancer therapy.
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