Details

Autor(en) / Beteiligte

• Wu, Wei
• Yang, Jun-Ling
• Wang, Yi-Lang
• Wang, Han
• Yao, Min
• Wang, Li
• Gu, Juan-Juan
• Cai, Yin
• Shi, Yun
• Yao, Deng-Fu

Titel

Reversal of multidrug resistance of hepatocellular carcinoma cells by metformin through inhibiting NF-κB gene transcription

Ist Teil von

• World journal of hepatology, 2016-08, Vol.8 (23), p.985-993

Ort / Verlag

United States: Baishideng Publishing Group Inc

Erscheinungsjahr

2016

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.