Sorafenib and vorinostat toxicity is enhanced by GX15-070 in SW480 cells.
A, HCT116 cells were, as indicated, infected with recombinant adenoviruses,
and 24 h after infection, cells were treated with vehicle, sorafenib,
vorinostat, or both drugs together. Forty-eight hours after exposure, cells
were isolated and stained with Annexin V-propidium iodide, and cell viability
was determined by flow cytometry (± S.E.M., n = 3).
*, p < 0.05 less than corresponding value in CMV vector
cells. Inset, expression of BCL-XL 24 h after infection. B, HCT116 cells were
treated with vehicle or GX15-070 followed by, as indicated, vehicle,
sorafenib, sodium valproate, or sorafenib + valproate. Twenty-four and 48 h
after exposure, cells were isolated and viability determined via Annexin
V-propidium iodide, and cell viability was determined by flow cytometry
(± S.E.M., n = 3 independent studies). #, p < 0.05
greater than corresponding value in HCT116 cells (compare
Fig. 1B). C, SW480 cells, 24 h
after plating in triplicate, were treated with vehicle or GX15-070 followed
by, as indicated, vehicle (DMSO), sorafenib, sodium valproate, or sorafenib +
valproate. Twenty-four and 48 h after exposure, cells were isolated and
viability determined via Annexin V-propidium iodide, and cell viability was
determined by flow cytometry (± S.E.M., n = 3 independent
studies). D, SW480 cells were transfected with siRNA molecules to knock down
CD95. Twenty-four hours after transfection, cells were treated with vehicle or
GX15-070 followed by, as indicated, vehicle, sorafenib, sodium valproate, or
sorafenib + valproate. Twenty-four and 48 h after exposure, cells were
isolated, and viability was determined via Annexin V-propidium iodide, and
cell viability was determined by flow cytometry (± S.E.M., n =
2 independent studies). *, p < 0.05 less than
corresponding value in siSCR transfected cells. E and F, OVCAR, SKOVIII, Rh30,
and Rh41 cells were treated with vehicle or GX15-070 followed by, as
indicated, vehicle, sorafenib, vorinostat, sodium valproate, sorafenib +
valproate, or sorafenib + vorinostat. Forty-eight hours after exposure, cells
were isolated and viability was determined via trypan blue exclusion assay
(± S.E.M., n = 3 independent studies). #, p < 0.05
greater than sorafenib + vorinostat value. G and H, OVCAR and Rh41 cells were
transfected with siRNA molecules to knock down CD95. Twenty-four hours after
transfection, cells were treated with vehicle or GX15-070 followed by, as
indicated, vehicle, sorafenib, sodium valproate, or sorafenib + valproate.
Twenty-four and 48 h after exposure, cells were isolated and viability was
determined via trypan blue exclusion assay (± S.E.M., n = 2
independent studies). *, p < 0.05 less than
corresponding value in siSCR-transfected cells.