[1]张言言,韩 刚,曹 羽,等.同源盒基因10调控胰岛素样生长因子结合蛋白3与肠癌细胞5-氟尿嘧啶抵抗的关系研究[J].陕西医学杂志,2022,51(7):771-775.[doi:DOI:10.3969/j.issn.1000-7377.2022.07.001]
 ZHANG Yanyan,HAN Gang,CAO Yu,et al.Relationship between regulation of IGFBP3 by HOXD10 and 5-fluorouracil resistance in colorectal cancer cells[J].,2022,51(7):771-775.[doi:DOI:10.3969/j.issn.1000-7377.2022.07.001]
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同源盒基因10调控胰岛素样生长因子结合蛋白3与肠癌细胞5-氟尿嘧啶抵抗的关系研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年7期
页码:
771-775
栏目:
基础研究
出版日期:
2022-07-05

文章信息/Info

Title:
Relationship between regulation of IGFBP3 by HOXD10 and 5-fluorouracil resistance in colorectal cancer cells
作者:
张言言韩 刚曹 羽张 云张 旭胡 建龚航军
(上海中医药大学附属曙光医院胃肠外科,上海 200021)
Author(s):
ZHANG YanyanHAN GangCAO YuZHANG YunZHANG XuHU JianGONG Hangjun
(Department of Gastrointestinal Surgery,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China)
关键词:
结直肠癌 5-氟尿嘧啶 化疗耐受 同源盒基因10 胰岛素样生长因子结合蛋白3
Keywords:
Colorectal cancer Fluorouracil Chemotherapy resistance HOXD10 IGFBP3
分类号:
R 735.3
DOI:
DOI:10.3969/j.issn.1000-7377.2022.07.001
文献标志码:
A
摘要:
目的:研究同源盒基因10(HOXD10)调控胰岛素样生长因子结合蛋白3(IGFBP3)与肠癌细胞5-氟尿嘧啶(5-Fu)抵抗的关系。方法:原代肠癌细胞SW480敲减HOXD10,5-Fu耐药株细胞过表达HOXD10及敲减IGFBP3。CCK-8检测细胞增殖活性,细胞克隆形成实验检测细胞克隆形成能力,实时荧光定量PCR(qPCR)及免疫蛋白印迹(WB)检测HOXD10及IGFBP3表达水平。结果:耐药株在各5-Fu浓度下(5、10、20 μg/ml)的增殖活性,与0 μg/ml的5-Fu增殖活性比较无统计学差异(均P>0.05); 而原代SW480细胞在5 μg/ml的增殖活性出现下降(P<0.01)。耐药细胞组HOXD10的相对表达倍数(0.51±0.096)与原代细胞组(1.00±0.091)比较下调,而耐药细胞组的IGFBP3相对表达倍数(4.21±0.32)显著高于原代细胞组(1.00±0.22),WB也证实了耐药细胞组较原代肠癌细胞组有较低的HOXD10和更高的IGFBP3表达水平。在原代细胞组中敲减HOXD10、IGFBP3的表达水平增高; 而在耐药细胞组中过表达HOXD10、IGFBP3的表达水平显著减低。在耐药株中敲减IGFBP3或过表达HOXD10后,耐药株对5-Fu敏感性增强,细胞克隆形成能力减弱。结论:HOXD10-IGFBP3调控轴与维持肠癌耐药表型密切相关,靶向抑制IGFBP3或过表达HOXD10可能在肠癌5-Fu化疗耐受提供精准干预靶点。
Abstract:
Objective:To study the relationship between regulation of IGFBP3 by HOXD10 and 5-fluorouracil(5-Fu)resistance in colorectal cancer cells.Methods:HOXD10 in primary colon cancer cell SW480 was knocked down.HOXD10 in 5-Fu resistant cell lines was over expressed,and IGFBP3 was knocked down.Cell proliferation activity was detected by CCK-8 assay,and cell clone formation ability was detected by cell clone formation experiment,and expression levels of HOXD10 and IGFBP3 were detected by real-time fluorescence quantitative PCR(qPCR)and Western blot(WB).Results:The proliferation activity of drug-resistant strains at various 5-Fu concentrations(5,10,20 μg/ml)was not significantly different from that of 0 μg/ml 5-Fu(all P>0.05).The proliferation activity of SW480 cells at 5 μg/ml decreased(P<0.01).The relative expression fold of HOXD10 in the drug-resistant cell group was down-regulated compared with the primary cell group(0.51±0.096 vs.1.00±0.091,P<0.05),while the relative fold of IGFBP3 expression in the drug-resistant cell group was significantly higher than that of the primary cell group(4.21±0.32 vs.1.00±0.22,P<0.05),WB also confirmed that the drug-resistant cell group had lower HOXD10 and higher IGFBP3 expression levels than the primary colon cancer cell group.Knockdown of HOXD10 in the primary cell group increased the expression level of IGFBP3.While over-expressing HOXD10 in the drug-resistant cell group,the expression level of IGFBP3 decreased significantly.After knocking down IGFBP3 or over-expressing HOXD10 in drug-resistant strains,the sensitivity of drug-resistant strains to 5-Fu was enhanced and the ability of cell clone formation was weakened.Conclusion:The HOXD10-IGFBP3 regulatory axis is closely related to the maintenance of the drug resistance phenotype of colorectal cancer.Targeted inhibition of IGFBP3 or over-expression of HOXD10 may provide precise intervention targets for 5-Fu chemotherapy resistance in colorectal cancer.

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备注/Memo

备注/Memo:
基金项目:上海市科学技术委员会科研计划项目(19401973000)
更新日期/Last Update: 2022-07-05