Astragaloside IV enhanced carboplatin sensitivity in prostate cancer by suppressing AKT/NF-κB signaling pathway.
Biochem Cell Biol. 2020 Aug 19. Epub 2020 Aug 19. PMID: 32813978
In our study, we explored the effect of AgIV on carboplatin chemotherapy in prostate cancer cell lines in vitro and in vivo. Cell viability assay, colony formation assay, flow cytometry, western blot, immunohistochemistry (IHC), immunofluorescence and tumor xenograft growth assay were conducted. We found that AgIV significantly decreased the half maximal inhibitory concentration (IC50) of carboplatin in prostate cancer cell lines LNCap and PC-3. Moreover, AgIV enhanced the effect of carboplatin in suppressing colony formation and inducing cell apoptosis. A low dose carboplatin treatment upregulated N-cadherin and Vimentin expression and downregulated E-cadherin expression, but this effect was abolished by combining with AgIV. Carboplatin treatment increased the levels of p-AKT and p-p65 and decreased p-IκBα, but AgIV treatment suppressed this. In addition, AgIV synergized with carboplatin to suppress tumor xenograft growth of PC-3 cells, and decreased pAKT and p-p65 levels in vivo. In summary, our results suggested that AgIV enhanced carboplatin sensitivity in prostate cancer cell lines by suppressing AKT/NF-кB signaling, thus suppressed EMT induced by carboplatin. Our findings provided a new mechanism for AgIV in overcoming drug resistance of platinum-based chemotherapy, and suggested a potential combination therapy of AgIV and carboplatin in prostate cancer.