title: [The effect and mechanism of vinorelbine on cisplatin resistance of human lung cancer cell line A549/DDP].
abstract: OBJECTIVE
  Drug resistance is a major obstacle on lung cancer treatment and Vinorelbine is an effective drug to inhibition of tumor proliferation and metastasis. In this study, we investigated the effect and mechanism of Vinorelbine on reversing the cisplatin resistance of human lung cancer A549/DDP cell line.
  
  
  METHODS
  With 1 μmol/L and 5 μmol/L Vinorelbine treatment, MTS assay was employed to determine the effect of the cisplatin sensitivity of tumor cells, flow cytometry to determine the apoptosis rate and change of Rh-123 content; Western blot to determine the expression of MDR1, Bcl-2, surviving, PTEN, caspase-3/8 and phosphorylation level of Akt (p-Akt); Real-time PCR was to determine the mRNA expression of MDR1, Bcl-2, survivin and PTEN. Finally the transcriptional activities of NF-κB, Twist and Snail were determined by reporter gene system.
  
  
  RESULTS
  With 1 μmol/L and 5 μmol/L Vinorelbine treatment, the sensitivity of cancer cells to cisplatin was increased by 1.91- and 2.54- folds respectively, flow cytometry showed that the content of Rh-123 was elevated 1.93- and 2.95- folds and apoptosis rate was increased 2.25- and 3.82- folds, Western blot showed that the expression of multidrug resistance related proteins MDR, Bcl-2 and survivin were downregulated, caspase-3/8 and PTEN was upregulated, phosphorylation of Akt was downregulated as well, real-time assay showed that the mRNA expression of MDR1 was downregulated 43.5% and 25.8%, Bcl-2 was downregulated 57.3% and 34.1%, survivin was downregulated 37.6% and 12.4%, PTEN was upregulated 183.4% and 154.2%, the transcriptional activities of NF-κB was downregulated 53.2% and 34.5%, Twist was downregulated 61.4% and 33.5%, and Snail was downregulated 57.8% and 18.7%.
  
  
  CONCLUSIONS
  Vinorelbine treatment led to increase of cisplatin sensitivity of A549/DDP cells and the mechanisms included the regulation of PTEN/AKT/NF-κB signal pathway to decreased drug resistance gene expression and increased pro-apoptosis gene expression.
authors.affiliation: Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China;Department of Pharmacy, Institute of Hematology, Blood Diseases Hospital Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Gao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D014747:Vinblastine; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3; D002945:Cisplatin; D000077235:Vinorelbine