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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 HepG 2 or HepG 2/adriamycin(ADM) cells treated with pC MV-NF-κB-small interference RNA(siR NA) 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 HepG 2 and HepG 2/ADM cells was closely related to mdr1 mR NA(3.310 ± 0.154) and NF-κB mR NA(2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siR NA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, Hep G2/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 siR NA were found in HepG 2/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 downregulating MDR1/P-gp expression.
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 and NF-κB in human HepG 2 or HepG 2 / adriamycin (ADM) cells treated with pC MV-NF-κB-small interference RNA (siR NA) 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 mR NA (3.310 ± 0.154) and NF-κB mR NA (2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siR NA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, Hep G2 / ADM cells were sensitized to d The synergistic effect of metformin and NF-κB siR NA were found in HepG 2 / ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis. CONCLUSION: Metformin via silencing NF-κB signaling could be a reverse MDR of HCC cells by downregulating MDR1 / P-gp expression.