| 摘要: |
| ［摘要］ 目的 探究染色质盒蛋白2（CBX2）在结直肠癌（CRC）进展及5-氟尿嘧啶（5-FU）耐药中的作用机制。方法 利用数据库及临床数据分析CBX2在CRC中的表达与临床病理特征的关系及对患者预后的影响。通过免疫组织化学染色、Western blot及实时荧光定量聚合酶链反应检测CRC样本中CBX2表达水平。构建CBX2下调及过表达的细胞模型并通过CCK-8实验、克隆形成实验、Transwell实验评价其对CRC细胞增殖、迁移、侵袭及对5-FU敏感性的影响。利用生物信息学分析并通过细胞实验验证CRC中CBX2对人肝配蛋白A受体-3（EphA3）/PI3K/AKT/mTOR信号通路的调控作用，以及对CRC细胞恶性生物学行为与对5-FU敏感性的影响。通过动物实验验证CBX2对CRC细胞体内成瘤能力的影响。结果 CBX2在CRC组织中高表达，其表达水平与肿瘤临床分期、肿瘤分化程度及淋巴结转移情况显著相关，CBX2阳性表达是CRC患者预后不良的危险因素。下调CBX2可抑制CRC细胞增殖、迁移、侵袭，并增强对5-FU的敏感性；过表达CBX2的作用则相反。CBX2可上调EphA3并与其直接结合，下调CBX2可降低EphA3表达并抑制PI3K/AKT/mTOR信号通路，抑制CRC细胞增殖、迁移、侵袭及对5-FU的敏感性。CBX2促进CRC细胞在裸鼠体内成瘤。结论 CBX2在CRC中高表达且与不良预后相关，其分子机制可能为CBX2通过与EphA3蛋白结合，激活PI3K/AKT/mTOR信号通路促进CRC细胞增殖、迁移、侵袭及5-FU耐药。 |
| 关键词: 结直肠癌 染色质盒蛋白2 人肝配蛋白A受体-3 5-氟尿嘧啶 耐药性 |
| DOI：10.3969/j.issn.1674-3806.2026.05.08 |
| 分类号:R 735.3 |
| 基金项目:广西自然科学基金项目（编号：2023GXNSFBA026003）；广西壮族自治区卫生健康委员会科研课题（编号：Z-A20220003） |
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| CBX2 promotes colorectal cancer progression and 5-FU resistance by upregulating EphA3 to activate the PI3K/AKT/mTOR signaling pathway |
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YU Zehao1, MO Chongde2, HOU Qiyan1, ZHAO Jiehua1, TANG Yi1, ZHANG Qiuhuan1
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1.Department of Colorectal and Anal Surgery, the People′s Hospital of Guangxi Zhuang Autonomous Region(Guangxi Academy of Medical Sciences), Nanning 530021, China; 2.Department of Hepatobiliary Surgery, the Sixth Affiliated Hospital of Guangxi Medical University, Yulin 537000, China
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| Abstract: |
| ［Abstract］ Objective To investigate the mechanisms of chromobox protein homolog 2(CBX2) in colorectal cancer(CRC) progression and 5-fluorouracil(5-FU) resistance. Methods The relationship between the expression of CBX2 in CRC and clinicopathological characteristics, as well as its impact on the patients′prognosis was analyzed by using databases and clinical data. The expression levels of CBX2 in CRC samples were detected by using immunohistochemical staining, Western blot and real-time fluorescent quantitative polymerase chain reaction( RT-qPCR). The CBX2 down-regulated and overexpressed cell models were constructed, and their effects on CRC cell proliferation, migration, invasion and sensitivity to 5-FU were evaluated by using CCK-8 assay, clone formation assay and Transwell assay. Bioinformatics analysis and cell experiments were conducted to verify the regulatory effects of CBX2 in CRC on the ephrin type-A receptor 3(EphA3)/PI3K/AKT/mTOR signaling pathway, as well as its influence on the malignant biological behavior of CRC cells and sensitivity to 5-FU. Animal experiments were conducted to verify the effect of CBX2 on the in vivo tumorigenic ability of CRC cells. Results CBX2 was significantly highly expressed in CRC tissues, and its expression level was significantly correlated with tumor clinical stage, tumor differentiation degree and lymph node metastasis. Positive expression of CBX2 was a risk factor for the CRC patients′ poor prognosis. Down-regulation of CBX2 could inhibit the proliferation, migration and invasion of CRC cells, and enhanced their sensitivity to 5-FU, while the effects of overexpressing CBX2 were the opposite. CBX2 could up-regulate EphA3 and bind it directly. Down-regulation of CBX2 reduced the expression of EphA3 and inhibited the PI3K/AKT/mTOR signaling pathway, thereby suppressing the proliferation, migration, invasion of CRC cells and their sensitivity to 5-FU. CBX2 promoted the tumorigenesis of CRC cells in nude mice. Conclusion CBX2 is highly expressed in CRC and is associated with poor prognosis. The molecular mechanisms may be related to that CBX2 promotes the proliferation, migration and invasion of CRC cells and their resistance to 5-FU by binding to the EphA3 protein and activating the PI3K/AKT/mTOR signaling pathway. |
| Key words: Colorectal cancer(CRC) Chromobox protein homolog 2(CBX2) Ephrin type-A receptor 3(EphA3) 5-fluorouracil(5-FU) Drug resistance |
