title: Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP.
abstract: BACKGROUND
  Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP.
  
  
  METHODS
  The cell viability was measured by MTT assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase II (Topo II) expressions in H446 and H446/VP cells after treated with or without VP-16.
  
  
  RESULTS
  The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo II were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo II expressions, and increase bax expression in H446 cells compared with that of H446/VP cells.
  
  
  CONCLUSIONS
  The H446/VP cell was stably resistant to VP-16. The decreased expression of Topo II was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.
authors.affiliation: Cell Biology Division, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wang
authors.forename: Yun-Li
authors.initials: YL
authors.lastname: Yan
authors.forename: Na-Jing
authors.initials: NJ
authors.lastname: Zhou
authors.forename: Shuo
authors.initials: S
authors.lastname: Han
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Zhao
authors.forename: Cui-Li
authors.initials: CL
authors.lastname: Cao
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Lü
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000378:metabolism*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004250:DNA Topoisomerases, Type II