PMC:6365940 / 31421-33331 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/6365940","sourcedb":"PMC","sourceid":"6365940","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6365940","text":"To determine if Nrf2 signaling was involved in digoxin-mediated reversing of gemcitabine resistance in SW1990/Gem and Panc-1/Gem cells, cells were transfected with Nrf2 shRNA (SW1990/Gem-shNrf2 and Panc-1/Gem-shNrf2). The protein levels of Nrf2, NQO1, HO-1, GCLC and ABCC5 were markedly reduced in SW1990/Gem-shNrf2 and Panc-1/Gem-shNrf2 cells (Fig. 7A–B and Supplementary Fig. S4E–F). Moreover, we found that the protein levels of Nrf2, NQO1, HO-1, GCLC and ABCC5 were no markedly changed in SW1990/Gem-shNrf2 and Panc-1/Gem-shNrf2 cells treated with digoxin (Fig. 7A–B and Supplementary Fig. S4E–F). In addition, we tested the sensitivity of SW1990/Gem-shNrf2 and Panc-1/Gem-shNrf2 cells to gemcitabine. Our results showed that SW1990/Gem and Panc-1/Gem cells with Nrf2 knockdown were more sensitive to gemcitabine than SW1990/Gem and Panc-1/Gem cells, respectively (Fig. 7C–D). However, the effects of digoxin were diminished in SW1990/Gem-shNrf2 and Panc-1/Gem-shNrf2 cells (Fig. 7C–D). In addition, Nrf2 overexpression plasmid were used to restore Nrf2 protein level in digoxin-treated gemcitabine-resistant pancreatic cancer cells, and found that gemcitabine resistance was restored (Supplementary Fig. S7). These data demonstrated that digoxin increased the sensitivity of SW1990/Gem and Panc-1/Gem cells to gemcitabine through inhibiting Nrf2 signaling.\nFig. 7 Digoxin increased the sensitivity of SW1990/Gem and Panc-1/Gem cells to gemcitabine by inhibiting Nrf2 signaling. (A–B) Effects of Nrf2 knockdown on protein levels of Nrf2, NQO1, HO-1, and GCLC in SW1990/Gem and Panc-1/Gem cells. (C–D) Effects of Nrf2 knockdown on reversing drug resistance of gemcitabine in SW1990/Gem and Panc-1/Gem cells. Data were expressed as mean ± SD, and the results were representative of three independent experiments. Significant differences were indicated as ***P \u003c 0.001 vs. control group. N.S., no significant.","divisions":[{"label":"label","span":{"begin":1362,"end":1368}}],"tracks":[]}