The reverse effect of X-ray irradiation on acquired gefitinib resistance in non-small cell lung cancer cell line NCI-H1975 in vitro

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• 作者：Jing Wang (1) (2)
  Hong Wei (1)
  Baoxia Zhao (2) (3)
  Mei Li (2)
  Weipeng Lv (1)
  Ling Lv (1)
  Bo Song (4)
  Shen Lv (1) (2)
  
• 关键词：Non ; small cell lung cancer ; Gefitinib ; Acquired resistance ; X ; ray irradiation ; Reverse effect ; EMT
• 刊名：Journal of Molecular Histology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：45
• 期：6
• 页码：641-652
• 全文大小：6,056 KB
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• 作者单位：Jing Wang (1) (2)
  Hong Wei (1)
  Baoxia Zhao (2) (3)
  Mei Li (2)
  Weipeng Lv (1)
  Ling Lv (1)
  Bo Song (4)
  Shen Lv (1) (2)
  
  1. Dalian Medical University, Dalian, 116044, People鈥檚 Republic of China
  2. Laboratory Center, Second Affiliated Hospital of Dalian Medical University, 467#, Zhongshan Road, Dalian, 116027, Liaoning Province, People鈥檚 Republic of China
  3. College of Medical Laboratory, Dalian Medical University, Dalian, 116044, People鈥檚 Republic of China
  4. Department of Pathology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, Liaoning Province, People鈥檚 Republic of China
  
• ISSN：1567-2387

文摘

The clinical efficacy of gefitinib in the treatment of non-small cell lung cancer (NSCLC) with mutations in exon 18, 19 or 21 of epidermal growth factor receptor (EGFR) is limited by the acquired resistance to the drug. To explore whether X-ray irradiation could reverse the acquired gefitinib resistance in NSCLC cell in vitro. We chose a human NSCLC cell line NCI-H1975 to establish acquired gefitinib-resistant cell line named as NCI-H1975/GR. NCI-H1975/GR was irradiated with X-ray and then named as NCI-H1975/GR/XR. In the three cell lines, subsequently cell growth curves and cell population doubling time were calculated by cell proliferation assay, the changes of cell viability were evaluated by trypan blue dye exclusion method and MTT assay, the cell cycle distribution and apoptosis were investigated by flow cytometry, the expressions of E-cadherin and vimentin used to indicate epithelial-mesenchymal transition (EMT) were determined by western blot analysis, the protein expressions in EGFR/KRAS/BRAF transduction pathway were detected by immunocytochemistry, and the mutations of EGFR, KRAS and BRAF were detected by high resolution melting analysis and direct sequencing. We found that the X-ray irradiation enhanced the growth inhibitory effects of gefitinib on the acquired gefitinib-resistant cell line. Of NCI-H1975/GR/XR following gefitinib treatment, the IC50 decreased significantly, the cell proportion of phase G0/G1 was slightly higher, and the apoptosis cell proportion was significantly higher than those of NCI-H1975/GR. In addition, the reversal of EMT being present in NCI-H1975/GR cells was likely appearing in NCI-H1975/GR/XR cells. These results indicated that the acquired gefitinib resistance could be reversed by X-ray irradiation in NSCLC cell line NCI-H1975 harboring both the L858R and T790M mutation in vitro.