RESUMO
We studied the effect of quercetin on ovarian adenocarcinoma SKOV-3 cell line and isogenic subline SKOV-3/CDDP resistant to the anticancer drug cisplatin. It was found that in resistant cells, quercetin in a concentration of 100 µM that causes a decrease in the cell viability suppressed the expression of genes encoding the key antioxidant enzymes (SOD2, CAT, GPX1, and HO-1), transcription factor Nrf2, and kinases of the PI3K/Akt/mTOR signaling pathway. In parental cells, quercetin, on the contrary, increased the expression of these genes. The results confirm the redox-dependent regulation induced by quercetin and its opposite nature in cisplatin-sensitive and cisplatin-resistant cancer cells.
Assuntos
Cisplatino , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Antioxidantes/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Apoptose , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genéticaRESUMO
The effect of curcumin on the resistance of SKOV-3 human ovarian adenocarcinoma cells to cisplatin was studied. It was found that curcumin induced "reversal" of cancer cells resistance, which was associated with suppression of the expression of genes encoding the key antioxidant enzymes (SOD1, SOD2, CAT, GPX1, and HO-1) and transcription factor Nrf2 and a decrease in the expression of genes encoding kinases of the PI3K/Akt/mTOR signaling pathway. The obtained results confirm the role of redox-dependent regulation in the "reversal" of cancer cells resistance to cisplatin.
