Sinomenine hydrochloride inhibits breast cancer metastasis by attenuating inflammation-related epithelial-mesenchymal transition and cancer stemness
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Xiao Li1, Pingping Li2, Chao Liu3, Yu Ren1, Xiaojiang Tang1, Ke Wang1, Jianjun He1
1Department of Breast Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China
2Translational Medical Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China
3Department of Vascular Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China
Jianjun He, email: [email protected]
Ke Wang, email: [email protected]
Keywords: sinomenine hydrochloride, breast cancer, metastasis, EMT, CSC
Received: July 04, 2016 Accepted: January 03, 2017 Published: January 10, 2017
Sinomenine hydrochloride (SH) has been investigated for its anti-tumor growth effect. We have previously reported that SH inhibited breast cancer cell proliferation via MAPKs signaling. However, whether SH could inhibit tumor metastasis has not been fully explored. In this study, we found that SH suppressed the metastasis potential of breast cancer cells. The wound healing and transwell assays showed that SH inhibited the migration and invasion ability of both 4T1 and MDA-MB-231 breast cancer cells. The orthotopic mouse model of 4T1 and the experimental mouse model of MDA-MB-231-luc (MDA-MB-231 cell line expressing firefly luciferase) demonstrated that SH treatment inhibited breast cancer metastasis by inhibiting epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties without obvious hepatotoxicity and renal toxicity. We also found that SH decreased spleen volume and weight in both mouse models, especially in the 4T1 mouse model. IL-6, a strong inflammatory factor causing EMT, was remarkably reduced. Overall, this anti-metastasis effect of SH could be possibly caused by attenuating inflammatory reaction, which led to inhibition of EMT and CSC characteristics of breast cancer cells. This study, together with our previous one, provides more evidence of SH as a potential drug for breast cancer therapy.
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