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Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL‐6/STAT3 signaling pathway
Author(s) -
Zhao Yue,
Yao Jing,
Wu XiaoPing,
Zhao Li,
Zhou YuXin,
Zhang Yi,
You QiDong,
Guo QingLong,
Lu Na
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22182
Subject(s) - wogonin , vimentin , cancer research , tumor microenvironment , a549 cell , epithelial–mesenchymal transition , metastasis , stat3 , biology , mmp2 , signal transduction , medicine , immunology , microbiology and biotechnology , cell , pathology , cancer , scutellaria baicalensis , immunohistochemistry , biochemistry , tumor cells , alternative medicine , traditional chinese medicine
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment facilitates tumor metastasis. Clinically, it will be a promising choice to suppress tumor metastasis by targeting inflammatory microenvironment. Our previous studies have demonstrated that wogonin (a bioflavonoid isolated from the traditional Chinese medicine of Huang‐Qin) possesses the anti‐metastatic and anti‐inflammatory activity, but we have little idea about its efficacy on inflammatory‐induced tumor metastasis and the mechanism underlying it. In this study, we focused on epithelial mesenchymal transition (EMT), the first step of tumor metastasis, to evaluate the effects of wogonin on tumor metastasis in inflammatory microenvironment. We found that wogonin inhibited THP‐1 conditioned‐medium‐ (CM‐) and IL‐6‐induced EMT by inactivating STAT3 signal. And in wogonin‐treated A549 cells which pretreated with THP‐1 CM or IL‐6, the expression level of E‐cadherin, an EMT negative biomarker, increased while that of N‐cadherin, Vimentin, and EMT‐related transcription factors including Snail and Twist decreased. Moreover, wogonin inhibited IL‐6‐induced phosphorylation of STAT3, prevented p‐STAT3 dimer translocation into the nucleus, and suppressed the DNA‐binding activity of p‐STAT3. Interestingly, similar results were obtained in the tumor xenografts mice, including downregulation of p‐STAT3, N‐cadherin, and Vimentin while up‐regulation of E‐cadherin. Wogonin also inhibit the metastasis of A549 cells in vivo. Taken all data together, we concluded that wogonin suppresses tumor cells migration in inflammatory microenvironment by inactivating STAT3 signal. © 2014 Wiley Periodicals, Inc.