Bufalin reverses acquired resistance to sorafenib by downregulating p-Akt via IRE1 activation.

Abstract

<p>(A) Huh7 and Huh7-Sora cells were cultured in complete medium, and the viability was examined after 24, 48, and 72 h in culture. (B) The above cells were exposed to increasing concentrations of sorafenib for 48 h. Untreated cells served as controls. Cell viability (%) was compared to the corresponding untreated cells. (C) The above cells were exposed to increasing concentrations of bufalin for 48 h. Untreated cells served as controls. Cell viability (%) was compared with the corresponding untreated cells. The black line indicates the IC50. (D) The lysates of cells from (A) were subjected to immunoblotting. Band densities were normalized to β-actin. The relative band density from Huh7 cells was defined as 1. (E) Huh7-Sora cells were transfected with control or IRE1 siRNA for 24 h and then incubated with 100 nM bufalin for 24 h. Cell lysates were immunoblotted, and the density of each band was measured. Band densities were normalized to β-actin. The relative band density from control cells was defined as 1. The data represent three independent experiments. N.S., not significant. “*” represents P<0.05, “**” represents P<0.001.</p