Fig. 4

Effects of siGRP78 modified exosomes on the growth of Sorafenib sensitive and resistant cancer cells. a HepG2 (left panel) and PLC (right panel) growth was measured by MTT assay after 48 h, (Sorafenib; 0.1, 0.5, 1 or 10 μg/ml of Exo-scrambled siRNA or Exo-siGRP78 exosomes; and 0.1, 0.5, 1 or 10 μg/ml of Exo-scrambled siRNA or Exo-siGRP78 modified exosomes combined with or without Sorafenib. The values were plotted as % of growth vs Ctrl (untreated cells). Each point represents the mean ± SEM of three independent experiments (*p < 0. 05, versus Sorafenib treatment). b Western blot analysis was performed on HepG2 and PLC cell lines, and their resistant cells treated for 48 h with Sorafenib, Sorafenib + scramble siRNA modified exosomes derived from BM-MSCs or siGRP78 modified exosomes + Sorafenib derived from BM-MSCs. Protein levels of GRP78 were evaluated. GAPDH as internal control. c qPCR showed the expression of GRP78 in HepG2 and PLC cell lines, and their resistant cells treated for 48 h with Sorafenib, Sorafenib + scramble siRNA modified exosomes or Sorafenib + siGRP78 modified exosomes derived from BM-MSCs. GAPDH as internal control. d The Subcutaneous orthotopic tumour growth in vivo assay showed the tumor size after different treatments (Control, Sorafenib, Exo-scramble siRNA + Sora and Exo-siGRP78 + Sora). Exo-siGRP78 + Sora significantly inhibited the the growth of sensitive or resistant cancer cells. (1) Control (PBS); (2) Sorafenib; (3) Exo-siGRP78 + Sora; (4) Exo-scramble siRNA + Sora, (n = 5 for each group, injections at 25 mg/kg, q.o.d). e The median tumor volume showed the antitumor efficacy of the different treatments (Control, Sorafenib, Exo-scramble siRNA + Sora and Exo-siGRP78 + Sora). Significant differences in terms of tumor volume were observed from day 14, Exo-siGRP78 + Sora versus Exo-scramble siRNA + Sora (*P < 0.05)