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极光激酶A和AKT抑制剂与辐射联合对结肠癌细胞的协同作用。

Synergistic effects of Aurora A and AKT inhibitors combined with radiation in colon cancer cells.

作者信息

Peng Qiuxia, Zhou Wei, Li Jie, Liu Danqing

机构信息

Department of Interventional Oncology and Vascular Medicine, Shuangliu District First People's Hospital, No. 149, Northwest Street, Dongsheng, Shuangliu District, Chengdu, Sichuan, China.

Department of Neurosurgery, Shuangliu District First People's Hospital, No. 149, Northwest Street, Dongsheng, Shuangliu District, Chengdu, Sichuan, China.

出版信息

Discov Oncol. 2025 May 12;16(1):733. doi: 10.1007/s12672-025-02562-8.

DOI:10.1007/s12672-025-02562-8
PMID:40353996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12069760/
Abstract

PURPOSE: This study aimed to investigate the synergistic effects of combining Aurora A and AKT inhibitors with radiation therapy on colon cancer cells and to elucidate the underlying mechanisms. METHODS: Human colon cancer cell lines HCT-15 and HCT-116 were treated with Alisertib (Aurora A inhibitor), MK2206 (AKT inhibitor), and radiation alone or in combination. Cell viability, cell cycle distribution, apoptosis, and DNA damage were analyzed using MTT assays, flow cytometry, Western blotting, and immunofluorescence staining, respectively. RESULTS: The combination of Alisertib and MK2206 with radiation significantly suppressed cell proliferation, induced pronounced G2/M phase arrest, and enhanced apoptosis compared to single-agent treatments. Western blot and immunofluorescence analyses revealed elevated γ-H2AX levels, indicating increased DNA double-strand breaks. CONCLUSION: The integration of Aurora A and AKT inhibitors with radiation therapy synergistically enhances anticancer effects by amplifying DNA damage, disrupting mitotic progression, and inducing apoptosis. This combination represents a promising strategy for overcoming treatment resistance in colon cancer.

摘要

目的：本研究旨在探讨极光激酶A（Aurora A）和蛋白激酶B（AKT）抑制剂与放射治疗联合应用对结肠癌细胞的协同作用，并阐明其潜在机制。 方法：采用Aurora A抑制剂Alisertib、AKT抑制剂MK2206，单独或联合照射处理人结肠癌细胞系HCT-15和HCT-116。分别使用MTT法、流式细胞术、蛋白质免疫印迹法和免疫荧光染色法分析细胞活力、细胞周期分布、细胞凋亡和DNA损伤情况。 结果：与单药治疗相比，Alisertib和MK2206与放射治疗联合应用显著抑制细胞增殖，诱导明显的G2/M期阻滞，并增强细胞凋亡。蛋白质免疫印迹法和免疫荧光分析显示γ-H2AX水平升高，表明DNA双链断裂增加。 结论：Aurora A和AKT抑制剂与放射治疗联合应用，通过放大DNA损伤、破坏有丝分裂进程和诱导细胞凋亡，协同增强抗癌效果。这种联合应用是克服结肠癌治疗耐药性的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/14db3366456e/12672_2025_2562_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/864984d7e051/12672_2025_2562_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/ebc0f047725c/12672_2025_2562_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/14db3366456e/12672_2025_2562_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/864984d7e051/12672_2025_2562_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/ebc0f047725c/12672_2025_2562_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9544/12069760/14db3366456e/12672_2025_2562_Fig3_HTML.jpg

相似文献

[1]
Synergistic effects of Aurora A and AKT inhibitors combined with radiation in colon cancer cells.

Discov Oncol. 2025-5-12

[2]
The Synergistic Anti-colon Cancer Effect of Aurora A Inhibitors and AKT Inhibitors Through PI3K/AKT Pathway.

Anticancer Agents Med Chem. 2023

[3]
MLN8054, a small molecule inhibitor of aurora kinase a, sensitizes androgen-resistant prostate cancer to radiation.

Int J Radiat Oncol Biol Phys. 2011-4-20

[4]
Induction of Mitotic Catastrophe via Inhibition of Aurora B by Ionizing Radiation With Additive of Mulberry Water Extract in Human Bladder Cancer Cells.

Integr Cancer Ther. 2018-11-15

[5]
Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA repair in colorectal cancer cells.

Oncol Rep. 2015-3

[6]
Inhibition of mitotic Aurora kinase A by alisertib induces apoptosis and autophagy of human gastric cancer AGS and NCI-N78 cells.

Drug Des Devel Ther. 2015-1-14

[7]
The combination of alisertib, an investigational Aurora kinase A inhibitor, and docetaxel promotes cell death and reduces tumor growth in preclinical cell models of upper gastrointestinal adenocarcinomas.

Cancer. 2012-9-12

[8]
Alisertib, an Aurora kinase A inhibitor, induces apoptosis and autophagy but inhibits epithelial to mesenchymal transition in human epithelial ovarian cancer cells.

Drug Des Devel Ther. 2015-1-9

[9]
The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells.

Drug Des Devel Ther. 2015-3-16

[10]
Timosaponin AIII Enhances Radiosensitivity in Breast Cancer through Induction of ROS-Mediated DNA Damage and Apoptosis.

Radiat Res. 2025-4-1

本文引用的文献

[1]
Evaluating the efficacy of PARP inhibitor in ARID1A-deficient colorectal cancer: A study.

Cancer Biomark. 2025-3

[2]
AURKA inhibition shows promise as a therapeutic strategy for ARID1A-mutant colorectal cancer.

Discov Oncol. 2024-10-14

[3]
Comparison of the Effectiveness of Radiotherapy with 3D-CRT, IMRT, VMAT and PT for Newly Diagnosed Glioblastoma: A Bayesian Network Meta-Analysis.

Cancers (Basel). 2023-12-3

[4]
Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression.

Cancer Discov. 2023-12-12

[5]
Selective vulnerability of ARID1A deficient colon cancer cells to combined radiation and ATR-inhibitor therapy.

Front Oncol. 2022-9-30

[6]
The Synergistic Anti-colon Cancer Effect of Aurora A Inhibitors and AKT Inhibitors Through PI3K/AKT Pathway.

Anticancer Agents Med Chem. 2023

[7]
Network Meta-analysis of First-Line Systemic Treatment for Patients With Metastatic Colorectal Cancer.

Cancer Control. 2021

[8]
The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.

Mol Biol Rep. 2021-8

[9]
Radiation therapy in head and neck cancer.

Saudi Med J. 2021-3

[10]
Targeting Aurora B kinase with Tanshinone IIA suppresses tumor growth and overcomes radioresistance.

Cell Death Dis. 2021-2-4

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