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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017-Oct

Ginkgetin inhibits growth of breast carcinoma via regulating MAPKs pathway.

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Jun Cao
Chuang Tong
Yanyan Liu
Jianguo Wang
Xiaoyan Ni
Mao-Ming Xiong

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概要

The purpose of present study was to investigate anti-tumor activity of Ginkgetin (GK) and its mechanism of action in breast cancer. The effects of GK on growth of human breast cancer cell lines MDA-MB-231, BT-474 and MCF-7 were examined by MTT assay. Cells apoptosis in MCF-7 cells were analyzed by TUNEL staining and annexin-V and propidium iodide double staining. The effects of GK on expression of apoptotic associated proteins and mitogen-activated protein kinases (MAPKs) were determined by western blotting. The results showed that GK significantly inhibited proliferation of MDA-MB-231, BT-474 and MCF-7 cells in vitro with time and dose dependent manners and induced apoptosis in MCF-7 cells. GK treatment obviously induced the tumor cells apoptosis and inhibited tumor growth in the MCF-7 xenograft nude mice. GK increased expression of Bax, cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, and decreased the levels of Bcl-2 and survivin in MCF-7 cells. Moreover, GK treatment up-regulated expression of phospho extracellular-related kinase (p-ERK), p-p38 and phospho Jun-amino-terminal kinase (p-JNK) in MCF-7 cells in vitro, and increased numbers of p-p38, p-JNK and p-ERK positive cells in the tumor tissue in vivo. Strikingly, treatment of p38 inhibitor (or JNK inhibitor; ERK inhibitor) significantly prevented GK induced growth inhibition and apoptosis in MCF-7 cells. Collectively, our data exhibit GK exerts well anticancer effects in breast cancer cells, which at least in part, is via activation of the MAPKs. Our results provide a new approach for the treatment of breast cancer.

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