Fig. 2.

Altered Nrf2-signaling pathway by Sorafenib in HepG2 cells. The reduction of Nrf2 (A) and Keap1 (B) expressions and Nrf2-transactivation activity (C) were associated with downregulation of Trx1 expression (D) and activity (E) in HepG2. Sorafenib (10 μM), VEGF (50 ng/ml) and SFN (10 μM) were administered 24 h after cell stabilization. The expression of Nrf2 and Keap1 in nuclear fraction, and Trx1 in cell lysate was measured by western-blot analysis as described in Material and Methods. Nrf2-transactivation activity was assessed using ARE-luc transfected HepG2 cells. pTK-Renilla was used as internal control vector. Trx1 activity was measured as detailed in Material and Methods. Data are expressed as mean ± SEM of 4 independent experiments. The groups with different letters (a, b, c, d or e) were significantly different (p ≤ 0.05).