Curcumin may reverse 5-fluorouracil resistance on colonic cancer cells by regulating TET1-NKD-Wnt signal pathway to inhibit the EMT progress.
Biomed Pharmacother
; 129: 110381, 2020 Sep.
Article
em En
| MEDLINE
| ID: mdl-32887024
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, ß-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-NKD2-WNT signal pathway to inhibit the EMT progress.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Proteínas Proto-Oncogênicas
/
Neoplasias do Colo
/
Resistencia a Medicamentos Antineoplásicos
/
Curcumina
/
Proteínas Adaptadoras de Transdução de Sinal
/
Via de Sinalização Wnt
/
Fluoruracila
/
Oxigenases de Função Mista
Idioma:
En
Revista:
Biomed Pharmacother
Ano de publicação:
2020
Tipo de documento:
Article