摘要： 目的探讨CDGSH铁硫结构域2 （CISD2）在结直肠癌组织中的表达、临床意义及其对5-氟尿嘧啶（5-FU）化疗敏感性的影响。方法采用实时荧光定量PCR （qRT-PCR）、免疫组化检测结直肠癌和癌旁组织中CISD2的表达，采用χ²检验分析结直肠癌组织中CISD2的表达与临床指标之间的关系； MTT评估CISD2对结直肠癌细胞5-FU敏感性的影响； Western blotting检测HCT116和HCT8人结直肠癌细胞自噬蛋白ATG5、Beclin 1和LC3-Ⅱ/Ⅰ，凋亡蛋白caspase-3表达情况。结果 qRT-PCR和免疫组化结果显示，与癌旁组织比较，结直肠癌组织CISD2的表达水平明显降低（P<0.001），且与患者肿瘤M分期相关（P<0.05）。MTT结果显示，与单纯5-FU处理组比较，过表达CISD2联合5-FU处理组细胞活力下降更显著（P<0.05）。Western blotting结果显示，与单纯5-FU处理组比较，过表达CISD2联合5-FU处理组细胞中ATG5、Beclin 1和LC3-Ⅱ/Ⅰ蛋白水平降低，而活化的caspase-3和p-AKT水平增加（均P<0.05）。结论结直肠癌中CISD2表达下调能增加5-FU的敏感性，此作用可能是经AKT信号逆转5-FU诱导的自噬而实现的。

结直肠癌组织中CISD2的表达及其对5-氟尿嘧啶化疗敏感性的影响

曹会茹¹, 徐阳¹, 王华德¹, 文普帅^1,2

1. 锦州医科大学 基础医学院病理生理学教研室, 辽宁 锦州 121001;
2. 锦州医科大学 生物人类学研究所, 辽宁 锦州 121001

收稿日期:2021-05-09出版日期:2022-05-30发布日期:2022-05-28
通讯作者:文普帅
作者简介:曹会茹(1996-),女,硕士研究生.
基金资助:辽宁省教育厅青年科技人才“育苗”项目（JYTQN201921）；锦州医科大学大学生创新课题（20201016001）


关键词: CDGSH铁硫结构域2, 结直肠癌, 5-氟尿嘧啶, 化疗敏感性
Abstract: Objective To explore the expression and clinical significance of CDGSH iron-sulfur domain 2 (CISD2) in colorectal cancer (CRC) and its influence on 5-fluorouracil (5-FU) chemosensitivity. Methods qRT-PCR and immunohistochemistry were used to detect the expression of CISD2 in CRC and adjacent tissues. The χ² test was used to analyze the relationship between the expression of CISD2 in CRC and clinical indicators. The MTT-based viability assay was used to evaluate the effects of CISD2 on the 5-FU sensitivity of CRC cells. Western blotting determined the expression of the protein including autophagy protein ATG5,Beclin 1,and the LC3-Ⅱ/Ⅰ apoptotic protein caspase-3 in HCT116 and HCT8 human CRC cells. Results qRT-PCR and immunohistochemistry revealed significantly lower expression of CISD2 in CRC tissues compared to adjacent tissues (P< 0.001),and the relationship of CISD2 expression and the M stage of the patient's tumor (P< 0.05). 5-FU significantly decreased the viability of cells overexpressed CISD2 (P< 0.05). 5-FU treatment of cells that overexpressed CISD2 also resulted in significantly decreased protein levels of ATG5,Beclin 1,and LC3-Ⅱ/Ⅰ,and significant increased protein levels of activated caspase-3 and phosphorylated-protein kinase B (AKT) (all P< 0.05). Conclusion Down-regulation of CISD2 expression in CRC can increase the sensitivity of 5-FU. This effect may be achieved by reversing 5-FU-induced autophagy mediated by AKT signaling.
Key words: CDGSH iron-sulfur domain 2, colorectal cancer, 5-fluorouracil, chemosensitivity
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