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.
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.
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。
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