title: Multidrug resistance-associated protein 3 and Bcl-2 contribute to multidrug             resistance by vinorelbine in lung adenocarcinoma.
abstract: Although cancer cells initially respond to vinorelbine (NVB), the acquisition             of resistance to the treatment is the main cause of chemotherapeutic failure in             lung cancer. The intrinsic mechanism of drug resistance induced by NVB in lung             cancer is not clear and tumor cell models to study NVB resistance have not been             widely studied. We previously established a NVB resistant cell line, Anip973/NVB,             derived from the Anip973 lung adenocarcinoma cell line. The aim of this study             was to investigate the molecular mechanisms involved in the resistance to NVB             in lung adenocarcinoma. Genetic profiles of Anip973/NVB and Anip973 cells were             compared by microarray analysis and qRT-PCR. Tumor xenografts were obtained by             grafting Anip973/NVB and Anip973 cells into nude mice and the xenograft response             to NVB or control treatment was evaluated. Morphological assessment of xenograft             tissues was performed by transmission electron microscopy (TEM). Immunohistochemistry             (IHC) was used to compare Bcl-2 and MRP3 protein expression in xenografts. Fifty-five             up-regulated genes and 88 down-regulated genes in Anip973/NVB cells compared with             Anip973 cells were identified by cDNA microarray analysis. Up-regulation of MRP3             and Bcl-2 was confirmed by qRT-PCR. NVB inhibits xenografts of Anip973 growth             but did not affect xenografts of Anip973/NVB growth. Ultrastructural changes observed             by TEM showed that NVB induces apoptosis in the Anip973-treated group but not             in the Anip973/NVB-treated group. Higher expression rates of Bcl-2 and MRP3 were             observed in Anip973/NVB xenograft cells compared with Anip973 xenograft cells             by IHC. In conclusion, in the present study, we identified a set of genes responsible             for multidrug resistance in Anip973/NVB cells. Among them, MRP3 and Bcl-2 may             participate in lung adenocarcinoma multidrug resistance induced by NVB.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150081, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Hong
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Yang
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.forename: Gong-Yan
authors.initials: GY
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077235:Vinorelbine; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014747:Vinblastine; D000077235:Vinorelbine; C114462:multidrug resistance-associated protein 3