Page 80 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第43卷第7期
·966 · Journal of Nanjing Medical University（Natural Sciences） 2023年7月

·临床研究·

锌转运体8对结肠癌奥沙利铂耐药的影响

李艳梅 ，王 超 ，张 宁 ，瞿文豪 ，贾立周 2*
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内蒙古医科大学附属医院消化内科，内蒙古 呼和浩特 010030；巴彦淖尔市医院中心实验室，内蒙古 巴彦淖尔 015000；
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右江民族医学院基础医学院，广西 百色 533000
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［摘 要］ 目的：筛选结肠癌中奥沙利铂耐药相关基因，并验证其对奥沙利铂治疗结肠癌疗效的影响。方法：从NCBI⁃GEO数
据库下载并综合分析数据集GSE42387，筛选奥沙利铂耐药相关基因；通过Ualcan和GEPIA数据库检测耐药相关基因在结肠癌
中的表达和对预后的影响；转染siRNA⁃ZIP8干扰结肠癌细胞SW620中锌转运体8（zinc transporter 8，ZIP8）表达；CCK⁃8实验检
测ZIP8表达降低后奥沙利铂对结肠癌细胞增殖抑制的影响；流式细胞术检测ZIP8表达降低后奥沙利铂对结肠癌细胞凋亡的
影响；对化疗前结肠癌组织标本进行免疫组织化学染色，评估ZIP8与化疗效果的关系。结果：筛选出ZIP8、NUPR1、SLC43A1
和TEME73共4个耐药相关基因；ZIP8在结肠癌组织中高表达（P < 0.05），且与患者预后相关（P=0.005）；在相同药物浓度下，
siZIP8组细胞的增殖抑制率明显高于siNC组（P < 0.05），siZIP8组中奥沙利铂诱导的细胞凋亡率显著高于siNC组（P < 0.05）；
ZIP8低表达的患者有更长的总生存期（P=0.001）和无病生存期（P < 0.001）。结论：ZIP8促进了结肠癌患者的奥沙利铂耐药性，
可作为预测患者化疗预后的指标之一。
［关键词］ 奥沙利铂；结肠癌；耐药；锌转运体8
［中图分类号］ R735.3 ［文献标志码］ A ［文章编号］ 1007⁃4368（2023）07⁃966⁃08
doi：10.7655/NYDXBNS20230709

Effect of zinc transporter 8 on oxaliplatin resistance in colon cancer

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LI Yanmei ，WANG Chao ，ZHANG Ning ，QU Wenhao ，JIA Lizhou 2*
1 Department of Gastroenterology ，Affiliated Hospital of Inner Mongolia Medical University ，Hohhot 010030 ；
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2 Department of Central Laboratory，Bayannur Hospital，Bayannur 015000；Basic College，Youjiang Medical College
for Nationalities，Bai’se 533000，China
［Abstract］ Objective：To screen genes related to oxaliplatin resistance in colon cancer and verify the influence of them on the
oxaliplatin treatment of colon cancer. Methods：Data set GSE42387 was downloaded from NCBI⁃GEO and analyzed comprehensively，
and oxaliplatin resistance genes were screened. Ualcan and GEPIA databases were used to detect the expression of drug⁃resistant genes
in colon cancer and their influence on prognosis. Transfection of siRNA⁃ZIP8 interfered with zinc transporter 8（ZIP8）expression in
colon cancer cell SW620. CCK⁃8 proliferation assay detected the effect of oxaliplatin on colon cancer cell proliferation inhibition after
ZIP8 expression was inhibited. Flow cytometry was used to detect the effect of oxaliplatin on colon cancer cell apoptosis after the
expression of ZIP8 was decreased. Immunohistochemical staining was performed on colon cancer tissue samples before chemotherapy
to evaluate the relationship between ZIP8 and chemotherapy effect. Results：Four drug⁃resistant genes（ZIP8，NUPR1，SLC43A1 and
TEME73）were selected. ZIP8 was highly expressed in colon cancer tissues（P < 0.05）and correlated with patient prognosis（P=
0.005）. Under the same drug concentration，the proliferation inhibition rate of the siZIP8 group was significantly lower than that in the
siNC group，the half inhibitory concentration of oxaliplatin in the siZIP8 group was lower than that in the siNC group（P < 0.05）.
Patients with low ZIP8 expression had longer overall survival（P=0.001）and disease⁃free survival（P < 0.001）. Conclusion：ZIP8
promotes oxaliplatin resistance in colon cancer patients and can be used as an indicator for the prognosis of chemotherapy.
［Key words］ oxaliplatin；colon cancer；drug resistance；zinc transporter 8
［J Nanjing Med Univ，2023，43（07）：966⁃973］

［基金项目］ 国家自然科学基金（82060438）
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通信作者（Corresponding author），E⁃mail：jializhou@bynesyy.com