Attenuation of MUC4 potentiates the anticancer activity of auranofin via regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells.

Attenuation of MUC4 potentiates the anticancer activity of auranofin via regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells. Oncol Rep. 2017 Jul 28;: Authors: Bae JS, Lee J, Park Y, Park K, Kim JR, Cho DH, Jang KY, Park SH Abstract Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2. Under the same conditions, the expression level of phosphorylated Akt was also downregulated leading to an increase of FOXO3 in the nucleus. Notably, auranofin treatment in SKOV3 cells also resulted in the downregulation of the expression levels of both Her2 and phosphorylated Akt. Thus, Her2 was identified as the common molecular target protein by siRNA transfection against MUC4. Western blot analysis of total and nuclear fraction lysates from SKOV3 cells revealed that attenuation of MUC4 combined with auranofin treatment in SKOV3 cells synergistically activated FOXO3 translocation from the cytoplasm to the nucleus through the regulation of the Her2/Akt/FOXO3 pathway. Attenuation of MUC4 by siRNA transfection potentiated the antitumor effect of auranofin which was examine...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research