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Volume 35 Issue 2
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Article Navigation >  Journal of Pharmaceutical Practice and Service  > 2017  >  35(2): 121-125

XIU Jianping, YANG Chaoai, LIU Xi’ao, PAN Qianyu, WEI Guangxu, WANG Weixing. Exploration of the role and mechanism of all-trans retinoic acid on activation and oxidative stress of hepatic stellate cell[J]. Journal of Pharmaceutical Practice and Service, 2024, 42(7): 291-296. doi: 10.12206/j.issn.2097-2024.202312054
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

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

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

  • Received Date: 2016-10-28
  • Rev Recd Date: 2017-01-09
  • 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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    [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.
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    [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.
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The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells

doi: 10.3969/j.issn.1006-0111.2017.02.006
  • 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
  • Received Date: 2016-10-28
  • Rev Recd Date: 2017-01-09

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.

XIU Jianping, YANG Chaoai, LIU Xi’ao, PAN Qianyu, WEI Guangxu, WANG Weixing. Exploration of the role and mechanism of all-trans retinoic acid on activation and oxidative stress of hepatic stellate cell[J]. Journal of Pharmaceutical Practice and Service, 2024, 42(7): 291-296. doi: 10.12206/j.issn.2097-2024.202312054
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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