title: [Effect of Src tyrosine kinase inhibition on the drug-resistance as well as MDR1 and LRP expression of the human cis-platinum-resistant lung cancer cell line A549/DDP].
abstract: BACKGROUND
  The aim of this study is to investigate the effect of Src tyrosine kinase inhibition on the drug-resistance as well as the expression of multidrug resistance 1 (MDR1) and lung resistance-related protein (LRP) of the human cis-platinum-resistant lung cancer cell line A549/DDP.
  
  
  METHODS
  4-Anilinoquirazoline was used to inhibit Src tyrosine kinase activity in A549/DDP. Western blot analysis was used to detect the Src tyrosine kinase activity. CellTiter-Glo assay was used to detect the drug sensitivity of tumor cells. Flow cytometry was used to detect the intracellular Rh-123 content. Western blot and real-time PCR assay were used to detect the expression of tumor MDR1 and LRP.
  
  
  RESULTS
  4-Anilinoquirazoline can down-regulate the cellular Src tyrosine kinase activity in A549/DDP. After treatment with 2.5 μM and 10 μM of 4-anilinoquirazoline, the cells became more sensitive to the drug and the reversal folds (RFs) of tumor cell sensitivity to the drug were 1.59- and 2.10-fold, respectively. The intracellular content of Rh-123 improved by 1.21- and 1.59-fold, respectively. The mRNA levels of MDR1 were 53.8% and 27.5% of the control, respectively. The mRNA level of LRP was 59.3% and 21.4% of the control, respectively. The expression of MDR1 and LRP protein significantly decreased.
  
  
  CONCLUSIONS
  The inhibition of Src tyrosine kinase activity in A549/DDP cells can reverse multi-drug resistance and increase the sensitivity of the cells to the drug. The mechanism may be related to the down-regulation of cellular MDR1 and LRP.
authors.affiliation: Department of Laboratory Medicine, Rizhao People's Hospital, Rizhao 276826, China. lujie_rz@yahoo.com.cn
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Tian
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D019061:src-Family Kinases; D002945:Cisplatin