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2016 ; 10
(ä): 1419-41
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Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via
downregulation of SATB1 and Wnt/?-catenin pathway
#MMPMID27143851
Ma X
; Yan W
; Dai Z
; Gao X
; Ma Y
; Xu Q
; Jiang J
; Zhang S
Drug Des Devel Ther
2016[]; 10
(ä): 1419-41
PMID27143851
show ga
BACKGROUND: The flavonoid baicalein, a historically used Chinese herbal medicine,
shows a wide range of biological and pharmaceutical effects, among which its
potent antitumor activity has raised great interest in recent years. However, the
molecular mechanism involved in the antimetastatic effect of baicalein remains
poorly understood. This study aimed to verify the inhibitory effects of baicalein
on metastasis of MDA-MB-231 human breast cancer cells both in vitro and in vivo,
as well as to investigate the related mechanisms. METHODS: MTT assay was used to
examine the inhibition of baicalein on proliferation of MDA-MB-231 cells. Wound
healing assay and the in vitro invasion assay was carried out to investigate the
effects of baicalein on migration and invasion of MDA-MB-231 cells, respectively.
In order to explore the effects of baicalein on tumor metastasis in vivo,
xenograft nude mouse model of MDA-MB-231 cells was established. Animals were
randomly divided into four groups (control, therapy group, and low-dose and
high-dose prevention group, n=6), and treated with baicalein as designed.
Following sacrifice, their lungs and livers were collected to examine the
presence of metastases. qRT-PCR and Western blot were performed to study the
effects of baicalein on expression of SATB1, EMT-related molecules, and
Wnt/?-catenin signaling components of MDA-MB-231 cells as well as the metastatic
tissue. Effects of baicalein on the expression of target proteins in vivo were
also analyzed by immunohistochemistry. RESULTS: Our results indicated that
baicalein suppressed proliferation, migration, and invasion of MDA-MB-231 cells
in a time- and dose-dependent manner. Based on assays carried out in xenograft
nude mouse model, we found that baicalein inhibited tumor metastasis in vivo.
Furthermore, baicalein significantly decreased the expression of SATB1 in
MDA-MB-231 cells. It suppressed the expression of vimentin and SNAIL while
enhancing the expression of E-cadherin. Baicalein also downregulated the
expression of Wnt1 and ?-catenin proteins and transcription level of
Wnt/?-catenin-targeted genes. CONCLUSION: Our results demonstrate that baicalein
has the potential to suppress breast cancer metastasis, possibly by inhibition of
EMT, which may be attributed to downregulation of both SATB1 and the
Wnt/?-catenin pathway. Taken together, baicalein may serve as a promising drug
for metastasis treatment of breast cancer.