Fig. 5: Overexpression of Ets-1 promotes sorafenib resistance.

Huh7-Ets-1 WT stable cells were treated with (+) or without (−) DOX for 24 hours to induce ectopic Ets-1 expression, followed by treatment with DMSO or sorafenib (6 µM) for 48 h and flow cytometry to detect apoptosis (A), mitochondrial damage (B), or caspase 3/7 activity (C). The bar graphs on the right of A–C represent the degree of apoptosis, mitochondrial damage, and caspase 3/7 activity respectively. Lanes 1 and 2 were treated without DOX and lanes 3 and 4 were treated with DOX, along with DMSO (lanes 1, 3) or sorafenib (lanes 2, 4). The data represent the mean ± S.D. of at least 4–6 independent experiments. D Huh7-Ets-1 WT stable cells treated with (+) or without (−) DOX for 24 h followed by treatment with DMSO or sorafenib (6 µM) for an additional 24 and 48 h were analyzed by western blots. Cl PARP cleaved PARP, Cl Caspase 3 cleaved caspase 3. E Huh7-Ets-1 WT cells pretreated with DOX followed by treatment with DMSO (−) or 6 µM sorafenib (+) for 72 h were analyzed by MTT assay. The data represent the mean ± S.D. of three independent assays. Significant differences were determined by t test and indicated as: *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001.