Sinomenine hydrochloride inhibits breast cancer metastasis by attenuating inflammation-related epithelial-mesenchymal transition and cancer stemness

// Xiao Li 1 , Pingping Li 2 , Chao Liu 3 , Yu Ren 1 , Xiaojiang Tang 1 , Ke Wang 1 , Jianjun He 1 1 Department of Breast Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China 2 Translational Medical Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China 3 Department of Vascular Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China Correspondence to: Jianjun He, email: chinahjj@163.com Ke Wang, email: 979915080@qq.com Keywords: sinomenine hydrochloride, breast cancer, metastasis, EMT, CSC Received: July 04, 2016      Accepted: January 03, 2017      Published: January 10, 2017 ABSTRACT 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.