title: Knockdown of NANOG enhances chemosensitivity of liver cancer cells to doxorubicin by reducing MDR1 expression.
abstract: Multidrug resistance (MDR) is one of the major reasons for the failure of liver cancer chemotherapy, and its suppression may increase the efficacy of chemotherapy. NANOG plays a key role in the regulation of embryonic stem cell self-renewal and pluripotency. Recent studies reported that NANOG was abnormally expressed in several types of tumors, indicating that NANOG is related to tumor development. However, the correlation between NANOG and liver cancer chemoresistance remains uncertain. In this study, RNA interfere technology was employed to knock down NANOG expression in HepG2 human liver cancer cells. We found that the knockdown of NANOG expression in NANOG siRNA-transfected HepG2 cells resulted in decreased colony formation rate and cell migration compared to control HepG2 cells. In addition, HepG2 cells were treated with doxorubicin to evaluate the chemosensitivity to doxorubicin. We found that the doxorubicin sensitivity of HepG2 cells was increased with downregulation of NANOG expression. The expression of MDR1 at both mRNA and protein levels was decreased in HepG2 cells when NANOG was knocked down. These findings suggest that the knockdown of NANOG in HepG2 human cells resulted in decreased MDR1 expression and increased doxorubicin sensitivity, and NANOG could be used as a novel potential therapeutic target to reverse multidrug resistance of liver cancer.
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xiao-Geng
authors.initials: XG
authors.lastname: Deng
authors.affiliation: Laboratory of Biomechanics and Physiology, Guangdong Provincial Institute of Sports Science, Guangzhou, Guangdong, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: He
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Gao
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Quan-Bo
authors.initials: QB
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ru-Fu
authors.initials: RF
authors.lastname: Chen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002465:Cell Movement; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000071317:Nanog Homeobox Protein
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D004317:Doxorubicin