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Clinical and Translational Oncology

, Volume 18, Issue 1, pp 18–26 | Cite as

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

  • L. Liu
  • Y. Qiao
  • C. Hu
  • Y. Liu
  • Y. Xia
  • L. Wang
  • B. Liu
  • H. Chen
  • X. Jiang
Research Article

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.

Keywords

Endostatin NSCLC VEGFR2 HIF-1α Radiosensitivity 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (NO. 81472792), Research Fund from Ministry of Health (W201210), and the National Natural Science Foundation of Jiangsu Province (BK2012661).

Conflict of interests

We have read and understood Clinical and Translational Oncology’s policy on disclosing conflicts of interest and declare that we have none.

Ethics statement

Our study did not refer to clinical trial and animal trial, so there was no ethics statement.

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2015

Authors and Affiliations

  • L. Liu
    • 1
  • Y. Qiao
    • 2
  • C. Hu
    • 2
  • Y. Liu
    • 1
  • Y. Xia
    • 2
  • L. Wang
    • 2
  • B. Liu
    • 1
  • H. Chen
    • 1
  • X. Jiang
    • 2
  1. 1.Xuzhou Medical College Graduate AcademyXuzhouChina
  2. 2.Department of Radiation OncologyLianyungang First People’s HospitalLianyungangChina

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