| 吴治州,王琛禹,肖云华,等.抑制极光激酶A促进125I粒子诱导的肝癌细胞有丝分裂灾难及辐射增敏[J].中华放射医学与防护杂志,2026,46(5):504-512.Wu Zhizhou,Wang Chenyu,Xiao Yunhua,et al.Inhibiting AURKA exacerbates mitotic catastrophe and enhances radiosensitivity of hepatocellular carcinoma cells to 125I seeds[J].Chin J Radiol Med Prot,2026,46(5):504-512 |
| 抑制极光激酶A促进125I粒子诱导的肝癌细胞有丝分裂灾难及辐射增敏 |
| Inhibiting AURKA exacerbates mitotic catastrophe and enhances radiosensitivity of hepatocellular carcinoma cells to 125I seeds |
| 投稿时间：2025-11-10 |
| DOI：10.3760/cma.j.cn112271-20251110-00394 |
| 中文关键词: 肝细胞癌 125I 有丝分裂灾难 极光激酶A 放射敏感性 |
| 英文关键词:Hepatocellular carcinoma 125I Mitotic catastrophe Aurora kinase A Radiosensitivity |
| 基金项目:重庆市自然科学基金(CSTB2022NSCQ-MSX1501,CSTB2023NSCQ-MSX0600,CSTB2024NSCQ-KJFZMSX0038) |
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| 中文摘要: |
| 目的 探究极光激酶A (AURKA)与肝癌细胞125I粒子放射敏感性的相关性及潜在的分子机制。方法 通过免疫荧光观察125I粒子照射后肝癌细胞HUH7的形态学变化;利用GeneCard、iProX及GENEMANIA数据库筛选125I放射增敏核心基因并开展功能注释;构建AURKA敲低的HUH7细胞系,通过克隆形成实验检测细胞增殖能力;将HUH7细胞分为对照组、AURKA特异性抑制剂MLN8237组(0.8 μmol/L,72 h)、125I组(6 Gy)及MLN8237+125I组,通过免疫荧光、蛋白质免疫印迹、平板克隆、流式细胞术分别检测γ-H2AX表达、细胞增殖克隆能力、有丝分裂灾难发生率及凋亡情况。结果 免疫荧光显示,125I粒子辐射诱导肝癌细胞发生有丝分裂灾难;GeneCard、iProX及GENEMANIA数据库分析提示,AURKA与肝癌有丝分裂调控、不良预后相关(总生存期HR=1.9,95%CI:1.2~2.8;无病生存期HR=1.6,95%CI:1.1~2.3,P < 0.05),iProX数据库提示,AURKA可能参与125I照射诱导的有丝分裂灾难调控;与对照组相比,敲低AURKA可显著降低肝癌细胞增殖克隆能力(t=10.15,P < 0.05);与125I组相比,MLN8237+125I组γ-H2AX焦点数显著升高(t=5.76,P< 0.05),γ-H2AX蛋白表达量显著升高(t=16.26,P< 0.05);与NC-SH+125I组相比,SH-AURKA+125I组有丝分裂灾难率明显增加(t=7.76,P< 0.05),与125I组相比,MLN8237+125I组有丝分裂灾难率与凋亡率明显增加(t=10.39、6.27,P< 0.05)。结论 AURKA高表达与肝癌不良预后相关,敲低或通过MLN8237抑制AURKA,可通过加剧DNA双链断裂、提高有丝分裂灾难发生率增强肝癌细胞对125I粒子的放射敏感性。 |
| 英文摘要: |
| Objective To investigate the correlation between Aurora kinase A (AURKA) and the radiosensitivity of hepatocellular carcinoma (HCC) cells to 125I seeds, and to explore the potential molecular mechanism. Methods Morphological changes of HCC HUH7 cells after 125I seed irradiation were observed by immunofluorescence. The GeneCard, iProX and GENEMANIA databases were used to screen core genes for radiosensitization by 125I radiotherapy and perform functional annotation. An AURKA-knockdown HUH7 cell line was constructed, and cell colony-forming ability was assessed by plate colony formation assay. HUH7 cells were divided into control group, MLN8237 group (0.8 μmol/L, 72 h), 125I group (6 Gy), and MLN8237 + 125I group. Immunofluorescence, Western blot, plate colony formation, and flow cytometry were used to detect γ-H2AX expression, cell proliferation and colony formation, mitotic catastrophe rate, and apoptosis, respectively. Results Immunofluorescence showed that 125I seed irradiation induced mitotic catastrophe in HCC cells. Analysis of GeneCard, iProX, and GENEMANIA databases indicated that AURKA was associated with mitotic regulation and poor prognosis in HCC (overall survival: HR=1.9, 95% CI: 1.2-2.8; disease-free survival: HR=1.6, 95% CI: 1.1-2.3, P<0.05). The iProX database suggested that AURKA might be involved in the regulation of mitotic catastrophe induced by 125I irradiation. Compared with the control group, AURKA knockdown significantly reduced the proliferation and colony-forming ability of HCC cells (t=10.15, P<0.05). Compared with the 125I group, the number of γ-H2AX foci (t=5.76, P<0.05) and γ-H2AX protein expression (t=16.26, P<0.05) were significantly increased in the MLN8237 + 125I group. Compared with the NC-SH+125I group, the SH-AURKA+125I group exhibited a significantly increased mitotic catastrophe rate (t=7.76, P<0.05). Compared with the 125I group, the MLN8237+125I group showed significantly increased mitotic catastrophe and apoptosis rates (t=10.39 and 6.27, respectively; P< 0.05). Conclusion High AURKA expression is associated with poor prognosis in liver cancer. Knockdown or pharmacological inhibition of AURKA by MLN8237 enhances the radiosensitivity of liver cancer cells to 125I seeds by exacerbating DNA double-strand breaks and increasing the mitotic catastrophe rate. |
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