L Liu1, Y Qiao2, C Hu2, Y Liu1, Y Xia2, L Wang2, B Liu1, H Chen1, X Jiang3. 1. Xuzhou Medical College Graduate Academy, Xuzhou, 221006, China. 2. Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China. 3. Department of Radiation Oncology, Lianyungang First People's Hospital, No. 182, Tongguan Road, Lianyungang, 222002, Jiangsu, China. jxdysy1970@163.com.
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.
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: Fei Yang; Ximing Tang; Erick Riquelme; Carmen Behrens; Monique B Nilsson; Uma Giri; Marileila Varella-Garcia; Lauren A Byers; Heather Y Lin; Jing Wang; Maria G Raso; Luc Girard; Kevin Coombes; J Jack Lee; Roy S Herbst; John D Minna; John V Heymach; Ignacio I Wistuba Journal: Cancer Res Date: 2011-07-01 Impact factor: 12.701
Authors: S Grosso; J Doyen; S K Parks; T Bertero; A Paye; B Cardinaud; P Gounon; S Lacas-Gervais; A Noël; J Pouysségur; P Barbry; N M Mazure; B Mari Journal: Cell Death Dis Date: 2013-03-14 Impact factor: 8.469