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缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究

王婧,  方宏亮,  黄金路,  郭澄

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文章导航 > 药学实践与服务  > 2017 >  35(2): 121-125
王婧, 方宏亮, 黄金路, 郭澄. 缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究[J]. 药学实践与服务, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
引用本文: 王婧, 方宏亮, 黄金路, 郭澄. 缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究[J]. 药学实践与服务, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
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WANG Jing, FANG Hongliang, HUANG Jinlu, GUO Cheng. The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
Citation: WANG Jing, FANG Hongliang, HUANG Jinlu, GUO Cheng. The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
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缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究

doi: 10.3969/j.issn.1006-0111.2017.02.006
  • 1.

    上海交通大学附属第六人民医院, 上海 200233

  • 2.

    第二军医大学基础部免疫学教研室, 上海 200433

基金项目: 上海交通大学医学院医院药学科研基金青年项目（JDYX2016QN008）；上海交通大学医工交叉研究基金项目（YG2014QN08）

The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells

  • 1.

    Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200233, China

  • 2.

    Department of Immunology, Faculty of Basic Medicine, Second Military Medical University, Shanghai 200433, China

  • 摘要: 目的 研究缺失错配修复基因MLH1（MutL homolog 1）的结直肠癌细胞HCT-116对氟尿嘧啶（5-Fu）耐药机制。 方法 通过构建MLH1缺失的结直肠癌细胞HCT-116稳定表达MLH1细胞株，CCK-8试剂检测细胞恢复MLH1表达后对化疗药物5-Fu耐药性的影响，并通过流式细胞仪检测细胞表面干细胞标志CD133和分化标志CK20以及CK8的表达变化。 结果 HCT-116稳定表达MLH1分子后，其对5-Fu作用的化疗耐受性降低，5-Fu处理后细胞的活率显著降低（P<0.01）；流式细胞仪检测结果显示CD133表达显著降低，并伴随细胞分化标志CK8和CK20表达上调。 结论 结直肠癌细胞缺失错配修复基因MLH1引起5-Fu耐药性可能与其促进肿瘤干细胞样特性密切相关。
    Abstract: Objective To study the mechanisms of the drug resistance of DNA mismatch repair (MMR) deficient colorectal cancer (CRC) HCT-116 to 5-fluorouracil (5-Fu). Methods MLH1 deficiency HCT-116 cells were transfected with pcDNA3.1-MLH1 Vector.The expression of MLH1 was detected by Western blot.The change of resistance against 5-Fu was examined by detecting the cell viability with CCK-8 kits.The expression of CD133 (cancer stem cell marker) and CK8 & CK20 (cell differentiation marker) were detected by flow cytometry. Results Comparing to HCT-116 control group, the viability of HCT-116 cells was markedly decreased (P<0.01) after stable expressing MLH1, accompanied by the down-regulated expression of CD133 on the cell surface.Moreover, the up-regulation of cell differentiation marker CK8 and CK20 was observed in HCT-116 cells with stable expressing MLH1. Conclusion Our data indicated that the expression of MLH1 was associated with down-regulated CD133+ stem-like cells in colorectal cancer HCT-116 with MLH1 deficiency.Therefore, CD133+ stem-like cells may related to the drug resistance of MMR deficiency tumor.This study provides a possible theory to explain the 5-FU resistance in the colorectal cancer patients with MMR deficiency.
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  • 收稿日期:  2016-10-28
  • 修回日期:  2017-01-09

缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究

doi: 10.3969/j.issn.1006-0111.2017.02.006
  • 1. 上海交通大学附属第六人民医院, 上海 200233
  • 2. 第二军医大学基础部免疫学教研室, 上海 200433
    • 基金项目:  上海交通大学医学院医院药学科研基金青年项目（JDYX2016QN008）；上海交通大学医工交叉研究基金项目（YG2014QN08）
  • 收稿日期: 2016-10-28
  • 修回日期: 2017-01-09

摘要: 目的 研究缺失错配修复基因MLH1（MutL homolog 1）的结直肠癌细胞HCT-116对氟尿嘧啶（5-Fu）耐药机制。 方法 通过构建MLH1缺失的结直肠癌细胞HCT-116稳定表达MLH1细胞株，CCK-8试剂检测细胞恢复MLH1表达后对化疗药物5-Fu耐药性的影响，并通过流式细胞仪检测细胞表面干细胞标志CD133和分化标志CK20以及CK8的表达变化。 结果 HCT-116稳定表达MLH1分子后，其对5-Fu作用的化疗耐受性降低，5-Fu处理后细胞的活率显著降低（P<0.01）；流式细胞仪检测结果显示CD133表达显著降低，并伴随细胞分化标志CK8和CK20表达上调。 结论 结直肠癌细胞缺失错配修复基因MLH1引起5-Fu耐药性可能与其促进肿瘤干细胞样特性密切相关。

English Abstract

王婧, 方宏亮, 黄金路, 郭澄. 缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究[J]. 药学实践与服务, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
引用本文: 王婧, 方宏亮, 黄金路, 郭澄. 缺失错配修复基因MLH1的结直肠癌HCT唱116细胞对氟尿嘧啶耐药机制的研究[J]. 药学实践与服务, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
shu
WANG Jing, FANG Hongliang, HUANG Jinlu, GUO Cheng. The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
Citation: WANG Jing, FANG Hongliang, HUANG Jinlu, GUO Cheng. The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(2): 121-125. doi: 10.3969/j.issn.1006-0111.2017.02.006
shu

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