Chemoresistance to gemcitabine in hepatoma cells induces epithelial-mesenchymal transition and involves activation of PDGF-D pathway
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Qiong Wu1,*, Rui Wang1,*, Qingling Yang2, Xin Hou1, Sulian Chen2, Yueyue Hou1, Changjie Chen2, Yan Yang1, Lucio Miele4, Fazlul H Sarkar 5, Yuqing Chen3, Zhiwei Wang6,7
1 Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
2 Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, China.
3 Department of Respiration, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
4 University of Mississippi Cancer Institute, Jackson, MS, USA
5 Department of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI
6 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, MA, USA
7 The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China
* These authors contributed equally
Zhiwei Wang, email:
Yuqing Chen, email:
Keywords: Hepatocellular carcinoma; chemoresistance; PDGF-D, EMT, gemcitabine.
Received: May 30, 2013 Accepted: October 5, 2013 Published: October 7, 2013
Hepatocellular carcinoma (HCC) is one of the common malignances in the world and has high mortality in part due to development of acquired drug resistance. Therefore, it is urgent to investigate the molecular mechanism of drug resistance in HCC. To explore the underlying mechanism of drug resistance in HCC, we developed gemcitabine-resistant (GR) HCC cells. We used multiple methods to achieve our goal including RT-PCR, Western blotting analysis, transfection, Wound-healing assay, migration and invasion assay. We observed that gemcitabine-resistant cells acquired epithelial-mesenchymal transition (EMT) phenotype. Moreover, we found that PDGF-D is highly expressed in GR cells. Furthermore, down-regulation of PDGF-D in GR cells led to partial reversal of the EMT phenotype. Our findings demonstrated that targeting PDGF-D could be a novel strategy to overcome gemcitabine resistance in HCC.
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