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APR-246 增强结直肠癌对放疗的敏感性。

APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy.

机构信息

Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.

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.

出版信息

Mol Cancer Ther. 2023 Aug 1;22(8):947-961. doi: 10.1158/1535-7163.MCT-22-0275.

DOI:10.1158/1535-7163.MCT-22-0275
PMID:37216282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10390889/
Abstract

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. As there is currently no existing study on combining APR-246 with radiation in rectal cancer, our objective was to investigate whether APR-246 could enhance the sensitivity of colorectal cancer cells, regardless of their p53 status, to radiation treatment. The combination treatment had synergistic effects on HCT116p53-R248W/- (p53Mut) cells, followed by HCT116p53+/+ [wild-type p53 (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 with p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radiosensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in patients with rectal cancer.

摘要

p53 突变在直肠癌中很常见，与放射治疗抵抗高度相关。APR-246 作为一种小分子，可以恢复突变型 p53 的肿瘤抑制功能。由于目前尚无 APR-246 与直肠癌放疗联合的研究，我们的目的是研究 APR-246 是否可以增强结直肠癌细胞对放射治疗的敏感性，而与 p53 状态无关。联合治疗对 HCT116p53-R248W/-（p53Mut）细胞具有协同作用，其次是 HCT116p53+/+[野生型 p53（p53WT）]细胞，对 HCT116p53-/-（p53Null）细胞则表现出相加作用，通过抑制增殖、增强活性氧和促进凋亡。这些结果在斑马鱼异种移植模型中得到了验证。从机制上讲，与 p53Null 细胞相比，p53Mut 和 p53WT 细胞在联合治疗后具有更多被激活的通路和差异表达基因，尽管联合治疗在不同细胞系中调节了个别通路。APR-246 通过 p53 依赖和非依赖途径介导放射增敏作用。这些结果可能为直肠癌患者联合治疗的临床试验提供证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/2b6ec9bbdfe4/947fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/ab6beb1f7f79/947fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/bf0ca466b966/947fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/3086ae29e0a7/947fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/0b00aa66f413/947fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/136012383743/947fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/2b6ec9bbdfe4/947fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/ab6beb1f7f79/947fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/bf0ca466b966/947fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/3086ae29e0a7/947fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/0b00aa66f413/947fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/136012383743/947fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/10390889/2b6ec9bbdfe4/947fig6.jpg

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Oncogene. 2021 May;40(20):3533-3547. doi: 10.1038/s41388-021-01790-w. Epub 2021 Apr 29.
3
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