Fig. 8

HCC cell-derived exosomes affect sorafenib resistance via the HGF/c-Met/Akt pathway. a Elevated HGF levels in the cell culture supernatant contributed to sorafenib resistance induced by HCC cell-derived exosomes. HGF concentrations in the supernatant were determined by ELISA. Treatment of cells with HCC cell-derived exosomes for 48 h significantly increased HGF levels in the cell culture supernatant compared to that of the sorafenib group. The effects of MHCC-97H-derived exosomes were greater than those of MHCC-97 L-derived exosomes (* P <0.05). b HCC cell-derived exosomes increased the level of phosphorylated Met, Akt and VEGFR2 compared with that of sorafenib alone. c The increase in phosphorylated c-Met and Akt induced by MHCC-97H and MHCC-97 L derived exosomes was reduced by the c-Met inhibitor crizotinib (sora: sorafenib). d The increase in the levels of phosphorylated Akt induced by MHCC-97H- and MHCC-97 L-derived exosomes was weakened by the p-Akt inhibitor MK-2206 (sora: sorafenib)