期刊
ONCOLOGY REPORTS
卷 32, 期 6, 页码 2777-2788出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3520
关键词
berberine hydrochloride; proliferation; metastasis; apoptosis; interleukin-8; MDA-MB-231 cells; breast cancer
类别
资金
- Educational Commission of Shanghai of China [2012JW19]
- Key Research Innovation Project [13ZZ099]
- Key Project from the Department of Education of China [20123107130002]
- Shanghai Eastern Scholar Program [2013-59]
- Excellent Research Team Cultivation Program of Shanghai University of Traditional Chinese Medicine
Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-kappa B and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8-independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-kappa B. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of JAK2/PI3K/NF-kappa B/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.
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