title: Downregulation of NPM reverses multidrug resistance in human hepatoma cells via inhibition of P-glycoprotein expression.
abstract: Multidrug resistance (MDR) is an important issue in current cancer treatments. In human cancer, drug resistance is primarily associated with the overexpression of multidrug resistance gene 1 (MDR1). Therefore, the human MDR1 gene promoter may be a target for anti‑MDR drug screening. Numerous methods to prevent MDR have been investigated. However, they have been proven to be clinically ineffective. Therefore, the aim of the present study was to investigate whether downregulation of nucleophosmin (NPM) demonstrates any effects on the reversal of MDR in hepatocellular carcinoma (HCC) cells. In the present study, two in vitro MDR HCC cell lines, HepG2/Adriamycin (ADM) and SMMC7721/ADM, were established and the level of MDR was measured. The results demonstrated that NPM downregulation markedly reversed the effects of MDR in the model used. In addition, NPM downregulation reduced P-glycoprotein expression, as well as MDR1 expression. These results suggested that downregulation of NPM may be a novel and effective method of reversing the effects of MDR, and may be a potential adjuvant for tumor chemotherapy.
authors.affiliation: Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of General Surgery, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Blood Transfusion, Shanxi Academy of Medical Sciences Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: He
authors.affiliation: Department of General Surgery, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China.
authors.forename: Jiefeng
authors.initials: J
authors.lastname: He
authors.affiliation: Department of General Surgery, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China.
authors.forename: Yanzhang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of General Surgery, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China.
authors.forename: Haoliang
authors.initials: H
authors.lastname: Zhao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D007211:Indoles; C000716967:NPM1 protein, human; C530616:NSC 348884; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; D004317:Doxorubicin