Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy |
| |
| Authors: | Yang Heekyoung Yoon Su Jin Jin Juyoun Choi Seung Ho Seol Ho Jun Lee Jung-Il Nam Do-Hyun Yoo Hae Yong |
| |
| Institution: | aDepartment of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea;bSamsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea;cCancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea;dDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea |
| |
| Abstract: | The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity. |
| |
| Keywords: | Chk1 Chk1inhibitor AZD7762 Radiosensitivity DNA damage checkpoint |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
