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

• Published in: Oncotarget 2014-09, Vol.5 (18), p.8478-8491
• Main Authors: Wang, Jiabei, Yin, Dalong, Xie, Changming, Zheng, Tongsen, Liang, Yingjian, Hong, Xuehui, Lu, Zhaoyang, Song, Xuan, Song, Ruipeng, Yang, Haiyan, Sun, Boshi, Bhatta, Nishant, Meng, Xianzhi, Pan, Shangha, Jiang, Hongchi, Liu, Lianxin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - secondary; Cell Line, Tumor; Cell Movement - drug effects; Cytokine Receptor gp130 - metabolism; Epithelial-Mesenchymal Transition - drug effects; Female; Gene Expression Regulation, Neoplastic; Humans; Iron Chelating Agents - pharmacology; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice, Nude; Middle Aged; Neoplasm Invasiveness; Phosphorylation; Research Paper; RNA Interference; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; Thiosemicarbazones - pharmacology; Time Factors; Transfection; Transforming Growth Factor beta1 - pharmacology; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Xenograft Model Antitumor Assays
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.2328

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.