留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码
x 关闭 永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

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

downloadPDF
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
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

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.
  • [1] Brenner H,Kloor M,Pox CP.Colorectal cancer[J].Lancet,2014,383(9927):1490-1502.
    [2] Chen Q,Liu Z,Cheng L, et al.An analysis of incidence and mortality of colorectal cancer in China,2003~2007[J].China Cancer,2012,21(3):179-182.
    [3] Hsieh P,Yamane K.DNA mismatch repair:molecular mechanism,cancer,and ageing[J].Mech Ageing Dev,2008,129(7-8):391-407.
    [4] Hewish M,Lord CJ,Martin SA,et al.Mismatch repair deficient colorectal cancer in the era of personalized treatment[J].Nat Rev Clin Oncol,2010,7(4):197-208.
    [5] Sinicrope FA.DNA mismatch repair and adjuvant chemotherapy in sporadic colon cancer[J].Nat Rev Clin Oncol,2010,7(3):174-177.
    [6] Boland GM,Chang GJ,Haynes AB,et al.Association between adherence to National Comprehensive Cancer Network treatment guidelines and improved survival in patients with colon cancer[J].Cancer,2013,119(8):1593-1601.
    [7] 祝利民,沈克平,周浩,等.胃肠安及四藤方对人结肠癌细胞株干细胞CD133+的影响[J].上海交通大学学报(医学版),2016,36(2):161-165.
    [8] Taverna P,Liu L,Hanson AJ,et al.Characterization of MLH1 and MSH2 DNA mismatch repair proteins in cell lines of the NCI anticancer drug screen[J].Cancer Chemother Pharmacol,2000,46(6):507-516.
    [9] Rosen JM,Jordan CT.The increasing complexity of the cancer stem cell paradigm[J].Science,2009,324(5935):1670-1673.
    [10] Zeki SS,Graham TA,Wright NA.Stem cells and their implications for colorectal cancer[J].Nat Rev Gastroenterol Hepatol,2011,8(2):90-100.
    [11] O'Brien CA,Pollett A,Gallinger S,et al.A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J].Nature,2007,445(7123):106-110.
    [12] Ricci-Vitiani L,Lombardi DG,Pilozzi E,et al.Identification and expansion of human colon-cancer-initiating cells[J].Nature,2006,445(7123):111-115.
    [13] Dallas NA,Xia L,Fan F, et al.Chemoresistant colorectal cancer cells,the cancer stem cell phenotype,and increased sensitivity to insulin-like growth factor-I receptor inhibition[J].Cancer Res,2009,69(5):1951-1957.
    [14] Ma S,Lee TK,Zheng BJ,et al.CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway[J].Oncogene,2008,27(12):1749-1758.
    [15] Yasuda H,Tanaka K,Saigusa S,et al.Elevated CD133,but not VEGF or EGFR,as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer[J].Oncol Rep,2009,22(4):709-717.
    [16] Sinicrope FA,Mahoney MR,Smyrk TC, et al.Prognostic impact of deficient DNA mismatch repair in patients with stage Ⅲ colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy[J].J Clin Oncol,2013,31(29):3664- 3672.
    [17] Sargent DJ,Marsoni S,Monges G,et al.Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer[J].J Clin Oncol,2010,28(20):3219-3226.
  • [1] 桂明珠, 李静, 李志玲.  儿童伏立康唑的血药浓度与CYP2C19、CYP2C9和CYP3A5基因多态性的相关性研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402020
    [2] 黄韵, 张正银, 金英, 郑怡菁, 李铁军, 孙莉莉.  耐碳青霉烯类肺炎克雷伯菌及大肠埃希菌临床分离株耐药性及耐药基因分析 . 药学实践与服务, 2024, 42(10): 439-444. doi: 10.12206/j.issn.2097-2024.202309059
    [3] 王雪莲, 郑斯莉, 李志勇, 罗亨宇, 缪朝玉.  全身过表达人METRNL基因小鼠模型的构建与验证 . 药学实践与服务, 2024, 42(5): 198-202, 222. doi: 10.12206/j.issn.2097-2024.202311014
    [4] 姚瑞阳, 于海征, 李耀盺, 张磊.  丹参FBXL 基因家族的鉴定和表达模式分析 . 药学实践与服务, 2024, 42(11): 461-470. doi: 10.12206/j.issn.2097-2024.202407034
    [5] 宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅.  帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  2912
  • HTML全文浏览量:  325
  • PDF下载量:  497
  • 被引次数: 0
出版历程
  • 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

    全文HTML

参考文献 (17)

目录

    /

    返回文章
    返回

    版权所有：《药学实践与服务》编辑委员会

    主管、主办: 中国人民解放军海军军医大学地址: 上海市杨浦区国和路325号邮政编码: 200433

    电话: （021）81871324,81871397 E-mail: [email protected]

    网站备案号 沪ICP备05003363号-1

    本系统由 北京仁和汇智信息技术有限公司 开发    百度统计