The role and molecular mechanism of epithelial-mesenchymal transition in chemoresistance to oxaliplatin in colorectal cancer cells
10.3969/j.issn.1671-8348.2016.36.002
- VernacularTitle:EMT在大肠癌细胞奥沙利铂耐药中的作用及分子机制研究
- Author:
Debing XIANG
;
Hong DONG
;
Jin QUAN
;
Guiyin SUN
;
Mengxia LI
;
Dong WANG
- Keywords:
colorectal neoplasms;
epithelial cells;
oxaliplatin;
RNA,small interfering;
Snail
- From:
Chongqing Medicine
2016;45(36):5045-5048
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and molecular mechanism of epithelial‐mesenchymal transition (EM T ) in che‐moresistance to oxaliplatin in colorectal cancer cells .Methods Oxaliplatin resistant LOVO/L‐OHP cells were established by gradu‐ally increasing the concentration of oxaliplatin and intermittent treatment with high‐dose concentration on parental cells (LOVO) . The expression of E‐cadherin and Vimentin was detected by indirect immunofluorescence and Western blot analysis .The expression of Snail and Twist was detected by Western blot analysis .cell proliferation was detected by MTT .Results Compared with LOVO cells ,the epithelial phenotype of LOVO/L‐OHP cell line was lost ,and the expression of E‐cadherin was decreased (22 .63 ± 3 .25)% (P<0 .01) ,an increase in the mesenchymal marker Vimentin (475 .42 ± 58 .36)% (P< 0 .01) .LOVO/L‐OHP cell line Twist expression was slightly increased (116 .42 ± 18 .36)% (P> 0 .05) ,Snail expression was significantly increased (382 .18 ± 41 .33)% (P<0 .01) .The expression of siSnail increased E‐cadherin (246 .82 ± 31 .57)% (P<0 .01) .The expression of Vimentin (28 .75 ± 3 .96)% (P< 0 .01);siSnail significantly enhanced sensitivity to oxaliplatin based chemotherapy in LOVO/L‐OHP cell line ,IC50 control group and siSnail group were 23 .75 μg/mL and 12 .42 μg/mL .Conclusion EM T may play an important role in chemoresistance to oxaliplatin in colorectal cancer cells ,inhibition of EM T can restore chemosensitivity of resistant colorectal cancer cells.
