title: [Sequence-dependent effect of docetaxel with gefitinib on the proliferation and signal protein expression of human lung adenocarcinoma cell SPC-A1].
abstract: OBJECTIVE
  It has been proven that chemotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could not increase response for advanced non-small cell lung cancer (NSCLC), but its cellular mechanism was not well known. The aim of this study is to assess the effects of sequential administration of docetaxel and gefitinib on the cell proliferation and signal pathway of lung adenocarcinoma cell SPC-A1 and its cellular mechanism.
  
  
  METHODS
  The mutation of EGFR and K-ras gene were examined by qPCR-HRM. MTT assay was used to measure the cell proliferation. The expression and phosphorylation of EGFR, ERK, AKT and IGF-1R were determined by Western blot.
  
  
  RESULTS
  No EGFR or K-ras gene mutation was found in SPC-A1 cells. Compared with docetaxel or gefitinib alone, no synergistic effects on the cell proliferation were observed in cells treated with docetaxel and gefitinib concomitantly or gefitinib followed by docetaxel. However, sequential administration of gefitinib following docetaxel could remarkably increase the inhibition of docetaxel on cell proliferation. Docetaxel increased, and gefitinib decreased, the phosphorylation of EGFR and ERK respectively. The suppression of pEGFR and pERK induced by gefitinib could not be activated by docetaxel, whether simultaneously or subsequently. No significant effects on the expression of AKT and p-AKT were found when docetaxel and gefitinib were administered simultaneously or sequentially. Docetaxel decreased the expression of IGF-1R.
  
  
  CONCLUSIONS
  The phosphorylation of both EGFR and ERK, not the phosphorylation of AKT or the expression of IGFR, may contribute to the synergistic effects of EFGR-TKI following chemotherapy on the cell proliferation of NSCLC.
authors.affiliation: Department of Medical Oncology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Zhang
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jingxian
authors.initials: J
authors.lastname: Zheng
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000077192:Adenocarcinoma of Lung; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000077156:Gefitinib