title: Endostatin exerts radiosensitizing effect in non-small cell lung cancer cells by inhibiting VEGFR2 expression.
abstract: BACKGROUND
  To determine the effects of endostatin on vascular growth factor receptor 2 (VEGFR2) expression in non-small cell lung cancer (NSCLC) cells and the mechanisms underlying its radiosensitizing effect.
  
  
  METHODS
  VEGFR2 mRNA levels were determined in different NSCLC cell lines using qRT-PCR. RT-PCR and Western blot assays were used to assess the expression of mRNA and proteins. The radiosensitivity of the cells was determined by colony-formation assays; and cell apoptosis and cell cycle distribution were determined by flow cytometry.
  
  
  RESULTS
  VEGFR2 mRNA levels differed among the five NSCLC cell lines (P < 0.01), with the highest expression in Calu-1 cells and lowest in A549 cells. Endostatin significantly inhibited the growth of Calu-1 cells (P < 0.01) (IC20 = 296.5 μg/ml), and the expression of VEGFR2 and HIF-1α (P < 0.05). Phosphorylation of protein kinase B (Akt), extracellular signal-regulated kinases 1/2 (ERK1/2), and p38 were significantly lower in endostatin-treated cells than control (P < 0.05). Endostatin enhanced the radiosensitivity of Calu-1 cells to SER = 1.38 and induced apoptosis (P < 0.01) and G2/M blockage (P < 0.01). However, endostatin had limited effects on A549 cells. Compared with Calu-1 cells, there was not significantly effects on cell radiosensitivity (SER = 1.09).
  
  
  CONCLUSIONS
  Endostatin induces apoptosis and enhances radiosensitivity of the VEGFR2 high-expressing cell line Calu-1, but it has a limited effect on the VEGFR2 low-expressing cell line A549.
authors.affiliation: Xuzhou Medical College Graduate Academy, Xuzhou, 221006, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China.
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.affiliation: Xuzhou Medical College Graduate Academy, Xuzhou, 221006, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Xuzhou Medical College Graduate Academy, Xuzhou, 221006, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Xuzhou Medical College Graduate Academy, Xuzhou, 221006, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China. jxdysy1970@163.com.
authors.forename: X
authors.initials: X
authors.lastname: Jiang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D043169:Endostatins / Q000494:pharmacology*; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D043169:Endostatins; D011838:Radiation-Sensitizing Agents; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Endostatin; HIF-1α; NSCLC; Radiosensitivity; VEGFR2