αhederin overcomes hypoxiamediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway.
Int J Oncol
; 62(3)2023 03.
Article
en En
| MEDLINE
| ID: mdl-36704835
ABSTRACT
Currently, chemoresistance is a major challenge that directly affects the prognosis of patients with colorectal cancer (CRC). In addition, hypoxia is associated with poor prognosis and therapeutic resistance in patients with cancer. Accumulating evidence has shown that αhederin has significant antitumour effects and that αhederin can inhibit hypoxiamediated drug resistance in CRC; however, the underlying mechanism remains unclear. In the present study, viability and proliferation assays were used to evaluate the effect of αhederin on the drug resistance of CRC cells under hypoxia. Sequencing analysis and apoptosis assays were used to determine the effect of αhederin on apoptosis under hypoxia. Western blot analysis and reverse transcriptionquantitative PCR were used to measure apoptosisrelated protein and mRNA expression levels. Furthermore, different mouse models were established to study the effect of αhederin on hypoxiamediated CRC drug resistance in vivo. In the present study, the high expression of Bcl2 in hypoxic CRC cells was revealed to be a key factor in their drug resistance, whereas αhederin inhibited the expression of Bcl2 by reducing AKT phosphorylation in vitro and in vivo, and promoted the apoptosis of CRC cells under hypoxia. By contrast, overexpression of AKT reversed the effect of αhederin on CRC cell apoptosis under hypoxia. Taken together, these results suggested that αhederin may overcome hypoxiamediated drug resistance in CRC by inhibiting the AKT/Bcl2 pathway. In the future, αhederin may be used as a novel adjuvant for reversing drug resistance in CRC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Proteínas Proto-Oncogénicas c-akt
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
Pais de publicación:
GR
/
GRECIA
/
GREECE
/
GRÉCIA