盛兆瑛,蔡勇,倪健" /> The inhibitory effect of CL-387785 on the invasion and metastasis of T790M EGFR mutant H1975 cells and its sensitization of radiotherapy

Chinese Clinical Oncology

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The inhibitory effect of CL-387785 on the invasion and metastasis of T790M EGFR mutant H1975 cells and its sensitization of radiotherapy

SHENG Zhaoying, CAI Yong, NI Jian.
  

  1. Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China
  • Received:2015-04-29 Revised:2015-06-20 Online:2015-07-31 Published:2015-07-31

Abstract:

Objective To investigate the inhibitory effect of CL-387785 on the invasion and metastasis of EGFR T790M mutant H1975 cells and its sensitization of radiotherapy. Methods The H1975 cell was treated with 0,10, 25, 50, 100 nmol/L CL-387785. The MTT colorimetric assay was used to detect the proliferation inhibition rates at 24,48,72 and 96 h after treatment. Moreover,Annexin-FITC/PI double staining method via flow cytometry was used to detect the apoptotic rates of different concentrations of CL-387785 at 48 and 96 h. Changes of invasion and migration of H1975 cells treated with CL-387785 were detected by Transwell and scratch assay, respectively. The clone formation assay was employed to investigate the survival fraction(SF) of the H1975 cells after exposure to CL-387785 following different doses of X-ray (0, 2, 4, 6, 8 and 10 Gy) irradiation. The target model was fitted to the cell survival curve to calculate the sensitization enhancement ratio (SER). Results CL-387785 inhibited the proliferation of H1975 cells, and dose- and time-dependently increased the inhibition rates of the proliferation in range of 10-100 nmol/L. CL-387785 could induce the apoptosis and decrease the number of penetrate-membrane cell and migration distance of H1975 cells in a dose-dependent manner (P<0.05). In the 2-10 Gy irradiation range, the SF of 10, 25, 50 and 100 nmol/L CL-387785 were lower than that of 0 nmol/L,and SF decreased with the increase of concentration of CL-387785 and above differences were statistically significant (P<0.05). Compared with the 0 nmol/L CL-387785, the SER of 25, 50, 10, 100 nmol/L CL-387785 SER after treatment were 1.17, 1.39, 2.88 and 3.64, respectively. Conclusion The irreversible EGFR inhibitor CL-387785 can inhibit the invasion and metastasis of T790M EGFR mutant H1975 cells and has the effect of radiation sensitization.

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