Sirtuin 1 and 2 inhibitors enhance the inhibitory effect of sorafenib in hepatocellular carcinoma cells
- Ceballos Mancini, María Paula
- Angel, Antonella
- Delprato, Carla Beatriz
- Livore, Veronica Ines
- Ferretti, Anabela
- Lucci, Alvaro
- Comanzo, Carla Gabriela
- Alvarez, María de Luján
- Quiroga, Ariel Dario
- Mottino, Aldo Domingo
- Carrillo, Maria Cristina
DOIAbstract
Multidrug resistance (MDR) counteracts the efficiency of sorafenib, an important first-line therapy for hepatocellular carcinoma (HCC). Sirtuins (SIRTs) 1 and 2 are associated with tumor progression and MDR. We treated 2D and 3D cultures (which mimic the features of in vivo tumors) from HCC cells with sorafenib alone or in the presence of SIRTs 1 and 2 inhibitors (cambinol or EX-527; combined treatments). Cultures subjected to combined treatments showed a greater fall in cellular viability, proliferation (PCNA, cyclin D1 and Ki-67 expression and cell cycle analysis), migration and invasion when compared with cultures treated only with sorafenib. Similarly, combined treatments produced more apoptosis (annexin V/PI, caspase-3/7 activity) than...
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