Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 129, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.110381
Keywords
Curcumin; Colonic cancer; EMT; Wnt; 5-fluorouracil
Funding
- Zhejiang medical and health science and technology program [2016DTA001]
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Background and purpose: Colorectal cancer is a kind of gastrointestinal tumor with rising morbidity and mortality. 5-fluorouracil is one of the most effective chemotherapy drugs for the treatment of CRC. However, clinical data reported dramatic resistance on the treatment for CRC with 5-fluorouracil. Present study aims to explore the anti-resistant effect of curcumin and its mechanism. Methods: MTT assay was used to evaluate the proliferation of rHCT-116 cells. Flow cytometry was used to determine the apoptosis and cell cycle of rHCT-116 cells. Western Blot was performed to detect the expression level of TET1, NKD2, E-cadherin, Vimentin, beta-catenin, TCF4 and Axin in transfected rHCT-116 cells. Results: 5-fluorouracil resistant HCT-116 cells were successfully established. Curcumin was found to be effective in the inhibition of proliferation, inducement of apoptosis and block of G0/G1 phase on 5-fluorouracil treated HCT-116 cells. The expression of TET1 and NKD2 was greatly inhibited by high dosage of curcumin. The WNT signal pathway and EMT progress were suppressed in rHCT-116 cells by high dosage of curcumin. The inhibitory effects of curcumin on WNT signal pathway and EMT progress were verified to be consistent with Pax-6, TET1 and NKD2. Conclusion: Curcumin might exert anti-resistant effect of 5-FU on HCT-116 cells by regulating the TET1-NKD2WNT signal pathway to inhibit the EMT progress.
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