title: Chemoresistance to gemcitabine in hepatoma cells induces epithelial-mesenchymal transition and involves activation of PDGF-D pathway.
abstract: 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.
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Qingling
authors.initials: Q
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Hou
authors.forename: Sulian
authors.initials: S
authors.lastname: Chen
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Hou
authors.forename: Changjie
authors.initials: C
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D003841:Deoxycytidine; D000093542:Gemcitabine