Curcumin may reverse 5-fluorouracil resistance on colonic cancer cells by regulating TET1-NKD-Wnt signal pathway to inhibit the EMT progress - 28/08/20
, Runzhe Zhang d, 1, Xinjie Zhang d, Bo Zhang a, b, c, Qinghua Yao a, b, c, ⁎ Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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Graphical abstract |
Curcumin up-regulated the expression of TET1, which could also be promoted by its transcriptional mediator Pax-6 and in turns induced the expression of NKD2. The WNT signal pathway was inhibited by the high expressed NKD2 and EMT progress was suppressed. As a result, the migration and invasion of 5-FU resistance HCT-116 cells were inhibited. The present study claimed a possible signal pathway mechanism explaining the anti-resistant effects of curcumin against 5-FU resistance HCT-116 cells.
Highlights |
• | Curcumin enhanced the inhibitory effects of 5-FU against the cell growth of 5-FU resistant HCT-116 cells. |
• | WNT signal pathway in resistant HCT-116 cells was significantly inhibited by curcumin. |
• | We supposed that curcumin and Pax-6 might exert the same function on TET1. |
Abstract |
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, β-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.
El texto completo de este artículo está disponible en PDF.Keywords : Curcumin, Colonic cancer, EMT, Wnt, 5-fluorouracil
Esquema
Vol 129
Artículo 110381- septembre 2020 Regresar al número
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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