TABLE 1

Sorafenib synergizes with vorinostat to kill pancreatic tumor cells that is abolished by overexpression of c-FLIP-s

Pancreatic cancer (Mia Paca 2, PANC1, AsPc1) and hepatoma (HEP3B) cells were infected 12 h after plating at an approximate multiplicity of infection of 50 with either a control empty vector recombinant adenovirus (CMV) or a recombinant virus to express the caspase 8 inhibitor c-FLIP-s. Twenty-four hours after infection, infected cells were plated as single cells (250-1500 cells/well) in sextuplicate; 12 h after this plating, the infected cells were treated with vehicle (DMSO), sorafenib (3.0-6.0 μM), vorinostat (250-500 nM), or both drugs combined, as indicated, at a fixed concentration ratio to perform median dose-effect analyses for the determination of synergy. After drug exposure (48 h), the medium was changed, and cells were cultured in drug-free medium for an additional 10 to 14 days. Cells were fixed and stained with crystal violet, and colonies of >50 cells/colony were counted. Colony formation data were entered into the Calcusyn program, and combination index (CI) values were determined. A CI value of less than 1.00 indicates synergy.