| 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 |
| 投稿时间：2016-10-28 修订日期：2017-01-09 点此下载全文 |
| 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].药学实践杂志,2017,35(2):121~125 |
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| 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） |
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| 中文摘要: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。 |
| 中文关键词:结直肠癌 错配修复基因 化疗耐受 CD133 |
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| The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells |
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| 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. |
| keywords:colorectal cancers DNA mismatch repair drug resistance CD133 |
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