The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2 (NDRG2)/gp130/STAT3 pathway

// Jiabei Wang 1,* , Dalong Yin 1,* , Changming Xie 1,* , Tongsen Zheng 1,* , Yingjian Liang 1 , Xuehui Hong 1 , Zhaoyang Lu 1 , Xuan Song 1 , Ruipeng Song 1 , Haiyan Yang 1 , Boshi Sun 1 , Nishant Bhatta 1 , Xianzhi Meng 1 , Shangha Pan 1 , Hongchi Jiang 1 and Lianxin Liu 1,2 1 Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China 2 Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China * These authors contributed equally to this work Correspondence: Lianxin Liu, email: // Keywords : Dp44mT; NDRG2; hepatocellular carcinoma; metastasis; STAT3 Received : June 09, 2014 Accepted : August 07, 2014 Published : August 08, 2014 Abstract Here we showed that hepatocellular carcinoma (HCC) cell lines with high metastatic potential had low levels of NDRG2. The iron chelator Dp44mT up-regulated NDRG2, suppressed epithelial-mesenchymal transition (EMT) and inhibited tumor metastasis in HCC having high metastatic potential. Also Dp44mT attenuated the TGF-β1-induced EMT in HCC having low metastatic potential. In agreement, silencing endogenous NDRG2 with shNDRG2 in HCC cells attenuated the effect of Dp44mT. We showed that the NDRG2/gp130/STAT3 pathway can mediate Dp44mT effects. In agreement, we found that a combination of NDRG2 expression and p-STAT3 levels is a strong predictor of prognosis in HCC patients. We suggest that up-regulation of NDRG2 by Dp44mT is a promising therapeutic approach in HCC.