Journal of Radiation Research and Radiation Proces ›› 2016, Vol. 34 ›› Issue (1): 10202-010202.doi: 10.11889/j.1000-3436.2016.rrj.34.010202

• RADIOBIOLOGY AND RADIOMEDICINE • Previous Articles     Next Articles

TGF-β1 Inhibitors increasing the radiosensitivity of H460 lung cancer cells

HUANG Qianyi  ZHAO Yifan  JIANG Youqin  WANG Jingdong  YANG Hongying   

  1. (School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and
    Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, china)
  • Received:2015-10-22 Revised:2015-11-26 Online:2016-02-20 Published:2016-01-18
  • Contact: Ph.D. YANG Hongying, professor E-mail:yanghongying@suda.edu.cn
  • About author:HUANG Qianyi, female, was born in 1992. Now she is a master candidate of Department of Radiotherapy and Oncology, Second Affiliated Hospital, Soochow University, engaging in the field of radiation medicine. E-mail: qianyi.huang@qq.com
  • Supported by:

    Supported by National Natural Science Foundation of China (No. 31270898 and 11335011), the Key Program of Natural Science Foundation of Jiangsu Educational Committee (12KJA310005), the Priority Academic Program Development of Jiangsu Higher Education Institution (PARD), and Junzheng Scholarship of Soochow University (to HUANG Qianyi)

Abstract:

The purpose of this study was to investigate the radiosensitizing effect of SB431542, a selective inhibitor of TGF-β1 receptor, on H460 non-small-cell lung cancer cells and relative interfering effect on DNA damage response (DDR). Clonogenic assay was used to measure the radiosensitizing effects of SB431542 on H460 cells; xenograft mouse model was used to study the radiosensitization in vivo; flow cytometry was used to determine cell cycle distribution and apoptosis; immunofluorescence microscopy was used to assess 53BP1 foci and pospho-DNA-PKcs foci. The results showed that SB431542 could increase the radiosensitivity of H460 cells. Pretreatment of H460 cells with SB431542 prior to irradiation initiated fast DDR but inhibited DNA repair via non-homologous end joining pathway and thus resulting in more unrepaired DNA double strand breaks, which caused more severe cell cycle delay. However, apoptosis did not contribute to the radiosensitization. The data from xenograft model showed that compared with irradiation alone, the combination of SB431542 and 5 Gy of X-rays on three consecutive days significantly delayed the tumor growth from 5~12 d post treatment. All the above indicate that inhibition of TGF-β1 pathway using SB431542 prior to irradiation can attenuate DNA damage repair and disturb cell cycle distribution, leading to decreased clonogenic cell survival and tumor growth delay, which can be an effective adjunct in radiotherapy for certain lung cancer subtypes.

Key words: H460 cells, TGF-β1, Inhibitor SB431542, Radiosensitivity, DNA damage response

CLC Number: 

  • Q691,TL71