The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells
10.3969/j.issn.1006-0111.2017.02.006
- VernacularTitle:缺失错配修复基因MLH1的结直肠癌HCT-116细胞对氟尿嘧啶耐药机制的研究
- Author:
Jing WANG
1
;
Hongliang FANG
;
Jinlu HUANG
;
Cheng GUO
Author Information
1. 上海交通大学附属第六人民医院
- Keywords:
colorectal cancers;
DNA mismatch repair;
drug resistance;
CD133
- From:
Journal of Pharmaceutical Practice
2017;35(2):121-125
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanisms of the drug resistance of DNA mismatch repair (MMR) deficient color-ectal cancer (CRC) HCT-116 to 5-fluorouracil (5-Fu) .Methods MLH1 deficiency HCT-116 cells were transfected with pcD-NA3 .1-MLH1 Vector .The expression of MLH1 was detected by Western blot .The change of resistance against 5-Fu was ex-amined 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 expres-sion 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 resist-ance in the colorectal cancer patients with MMR deficiency .
