Additional file 5: of Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1–mediated inhibition of STAT3 and Akt/VEGFR2 pathway in hepatocellular carcinoma

Figure S5. PH potentiates the antitumor effect of Sor in HepG2 and SK-Hep1 xenografts. (A) HepG2 and SK-Hep1 xenografts were treated with PH (50mg/kg) or Sor (20mg/kg) or both and tumor growth was measured every 6 days. (B) No significant change in bodyweight was observed in treated groups (C) H and E images of heart, lung, liver and spleen showing no toxic effect of with PH treatment. (D) The in vivo SHP-1 phosphatase activity in PH (50 mg/kg) or Sor (20 mg/kg) or both treated tumors. (E) The protein levels of p-STAT3 and its downstream proteins in HepG2 and SK-Hep1 xenografts in vivo were determined by western blot. (G) Immunohistochemical staining (Left panel) of CD31, pSTAT-3, cleaved caspase-3, Ki67 and TUNEL in PH treated SK-Hep1 xenografts. Magnification: ×200. Quantifications of Immunostainings (Left Panel) Quantification of CD31+ vessel area per total tumor area. Quantification of pSTAT-3, cleaved caspase-3, TUNEL and Ki67 cells per high power field of view. Data represents mean values from five random fields per tumor section. Scale bar, 50 μm. Experiments were conducted in triplicate and mean values ± SD (bars) are shown. *p<0.05, and **p<0.01 versus control. (DOCX 529 kb)