Cholecystokinin attenuates radiation-induced lung cancer cell apoptosis by modulating p53 gene transcription.
The deregulation of p53 in cancer cells is one of the important factors by which cancer cells escape from the immune surveillance. Cholecystokinin (CCK) has strong bioactivity in the regulation of a number of cell activities. This study tests a hypothesis that CCK interferes with p53 expression to affect the apoptotic process in lung cancer (tumor) cells. In this study, tumor-bearing mice and A549 cells (a tumor cell line) were irradiated. The expression of CCK and p53 in tumor cells was assessed with RT-qPCR and Western blotting. The binding of p300 to the promoter of p53 was evaluated by chromatin immunoprecipitation. We observed that, with a given amount and within a given period, small doses/more sessions of irradiation markedly increased the levels of CCK in the sera and tumor cells, which were positively correlated with the tumor growth in mice and negatively correlated with tumor cell apoptosis. CCK increased the levels of histone acetyltransferase p300 and repressed the levels of nuclear factor-kB at the p53 promoter locus in tumor cells, which suppressed the expression of p53. In conclusion, CCK plays an important role in attenuating the radiation-induced lung cancer cell apoptosis. CCK may be a novel therapeutic target in the treatment of lung cancers.
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical UniversityBeijing 101149, China; Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149, China.
Yi
Y
Han
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical UniversityBeijing 101149, China; Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149, China.
Chongyu
C
Su
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Daping
D
Yu
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Shijie
S
Zhou
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Xiaoyun
X
Song
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Shuku
S
Liu
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Ming
M
Qin
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Yunsong
Y
Li
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University Beijing 101149, China.
Ning
N
Xiao
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical UniversityBeijing 101149, China; Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149, China.
Xiaoqing
X
Cao
Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing 101149, China.
Kang
K
Shi
Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing 101149, China.
Xu
X
Cheng
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical UniversityBeijing 101149, China; Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149, China.
Zhidong
Z
Liu
DNA remolding; Lung cancer; apoptosis; cholecystokinin; p53