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

Jiabei Wang; Dalong Yin; Changming Xie; Tongsen Zheng; Yingjian Liang; Xuehui Hong; Zhaoyang Lu; Xuan Song; Ruipeng Song; Haiyan Yang; Boshi Sun; Nishant Bhatta; Xianzhi Meng; Shangha Pan; Hongchi Jiang; Lianxin Liu

doi:10.18632/oncotarget.2328

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Research Papers:

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

Jiabei Wang, Dalong Yin, Changming Xie, Tongsen Zheng, Yingjian Liang, Xuehui Hong, Zhaoyang Lu, Xuan Song, Ruipeng Song, Haiyan Yang, Boshi Sun, Nishant Bhatta, Xianzhi Meng, Shangha Pan, Hongchi Jiang and Lianxin Liu _

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Oncotarget. 2014; 5:8478-8491. https://doi.org/10.18632/oncotarget.2328

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Abstract

Jiabei Wang1,*, Dalong Yin1,*, Changming Xie1,*, Tongsen Zheng1,*, Yingjian Liang 1, Xuehui Hong1, Zhaoyang Lu1, Xuan Song1, Ruipeng Song1, Haiyan Yang1, Boshi Sun1, Nishant Bhatta1, Xianzhi Meng1, Shangha Pan1, Hongchi Jiang1 and Lianxin Liu1,2

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.

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Research Papers:

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

Abstract