Association of Toxicity of Sorafenib and Sunitinib for Human Keratinocytes with Inhibition of Signal Transduction and Activator of Transcription 3 (STAT3)
Figure 5
Effects of sorafenib and sunitinib on MAPK activation in HaCaT cells and effects of MAPK inhibitor on sorafenib and sunitinib-induced cell growth inhibition and signal transduction.
(A) Alterations in MAPKs signal transduction. HaCaT cells were incubated in medium containing 1 µM sorafenib or sunitinib for the indicated times, followed by Western blot analysis using total cell lysates. (B) Effects of MAPK inhibitor on sorafenib- and sunitinib-induced cell growth inhibition. HaCaT cells were incubated with medium containing sorafenib at the indicated concentrations for 48 h after pretreatment with either U0126 (MEK1/2 inhibitor, 10 µM), SB203580 (p38 MAPK inhibitor, 10 µM), or DMSO (solvent) for 2 h. Cell viability was determined by WST-8 colorimetric assay. *p<0.01 (Student’s t-test) as compared with control (DMSO). Each bar represents mean ± SD (n = 4). (C) Alterations in STAT3 signal transduction in the presence of MAPK inhibitors. HaCaT cells were incubated in medium containing 1 µM sorafenib or sunitinib for the indicated times after pretreatment with 10 µM U0126 for 2 h or 10 µM SB203580 for 2 h, followed by Western blot analysis using total cell lysates.