机构：[1]Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.[2]Department of Gastrointestinal, Bariatric and Metabolic Surgery, Research Center for Nutrition, Metabolism & Food Safety, West China-PUMC C.C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.[3]Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[4]Department of Gastrointestinal Surgery, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.四川省人民医院[5]Department of Pathology, the First Hospital of Hebei Medical University, Hebei, China.[6]Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden.[7]Department of Medical Radiation Physics, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.[8]Department of Surgery, the First Hospital of Hebei Medical University, Hebei, China.
p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. There is no study on combining APR-246 with radiation in rectal cancer; therefore, we examined whether APR-246 sensitized colorectal cancer cells with different p53 status to radiation. The combination treatment had synergistic effects on HCT116p53-R248W/-(p53Mut) cells, followed by HCT116p53+/+(p53WT) cells, and exhibited an additive effect on HCT116p53-/-(p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared to p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radio-sensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in rectal cancer patients.
基金：
This work was supported by the grants from Swedish Cancer Foundation
(CAN2016/341 and 190322Pj), Liu Cancer (2020-0331 and 2020-11-25), Post-Doctor Research
Project of Sichuan University (Grant No.2022SCU12025) and Natural Science Foundation of
Sichuan Province (Grant No.2022NSFSC0764).
第一作者机构：[1]Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.[*1]Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden
推荐引用方式(GB/T 7714)：
Xie Xuqin,Fan Chuanwen,Luo Bin,et al.APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy[J].MOLECULAR CANCER THERAPEUTICS.2023,22(8):947-961.doi:10.1158/1535-7163.MCT-22-0275.
APA：
Xie Xuqin,Fan Chuanwen,Luo Bin,Zhang Jing,Jensen Lasse D...&Sun Xiao-Feng.(2023).APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy.MOLECULAR CANCER THERAPEUTICS,22,(8)
MLA：
Xie Xuqin,et al."APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy".MOLECULAR CANCER THERAPEUTICS 22..8(2023):947-961
