Endostatin exerts radiosensitizing effect in non-small cell lung cancer cells by inhibiting VEGFR2 expression

• L. Liu ^[1] ; Y. Qiao ^[2] ; C. Hu ^[3] ; Y. Liu ^[1] ; Y. Xia ^[3] ; L. Wang ^[3] ; B. Liu ^[1] ; H. Chen ^[1] ; X. Jiang ^[3]
  1. [1] Xuzhou Medical College

     Xuzhou Medical College

     China

     
  2. [2] Lianyungang First People’s Hospital, China
  3. [3] Lianyungang First People’s Hospital

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 18, Nº. 1, 2016, págs. 18-26
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.