Reversal of multidrug resistance of hepatocellular carcinoma cells by metformin through inhibiting NF-κB gene transcription.
World J Hepatol
; 8(23): 985-93, 2016 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-27621764
ABSTRACT
AIM:
To interfere with the activation of nuclear factor-κB (NF-κB) with metformin and explore its effect in reversing multidrug resistance (MDR) of hepatocellular carcinoma (HCC) cells.METHODS:
Expression of P-glycoprotein (P-gp) and NF-κB in human HepG2 or HepG2/adriamycin (ADM) cells treated with pCMV-NF-κB-small interference RNA (siRNA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR. Cell viability was tested by CCK-8 assay. Cell cycle and apoptosis were measured by flow cytometry and Annexin-V-PE/7-AnnexinV apoptosis detection double staining assay, respectively.RESULTS:
P-gp overexpression in HepG2 and HepG2/ADM cells was closely related to mdr1 mRNA (3.310 ± 0.154) and NF-κB mRNA (2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siRNA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, HepG2/ADM cells were sensitized to doxorubicin and P-gp was decreased through the NF-κB signaling pathway. The synergistic effect of metformin and NF-κB siRNA were found in HepG2/ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis.CONCLUSION:
Metformin via silencing NF-κB signaling could effectively reverse MDR of HCC cells by down-regulating MDR1/P-gp expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
World J Hepatol
Año:
2016
Tipo del documento:
Article
País de afiliación:
China