Fig. 7
GANT61 reversed the increase in Hedgehog signaling proteins and CD44 caused by sorafenib treatment. a Representative bright-field images of immunohistochemical staining for CD44, Gli1, Ptch1 and Shh in patient tumor samples showing low or high expression. Scale bar: 50 μm. b The result of immunohistochemical staining in a box diagram. c Immunofluorescence images of HCC PDOs after treatment with DMSO or GANT61 for 6 days. The cells were stained for CD44 (green) and stained with DAPI (blue). d The levels of CD44 and Hedgehog-related proteins in cell lines (SNU423 and BEL7402) grown as monolayer cells or spheroids. e Western blot analysis showed the levels of CD44 and Hedgehog-related proteins in cell lines (SNU423 and 7402) after treatment with DMSO (control), sorafenib, GANT61 or a combination of sorafenib and GANT61. f Western blot analysis showed the expression of MEKK2 and MEKK3 after sorafenib treatment at different concentrations in cell lines (SNU423 and BEL7402). g Illustration of the GANT inhibits Gli1to reverse the resistance of sorafenib in HCC. (*p < 0.05, ** p < 0.01, *** p < 0.001, P < 0.05 is considered statistically significant)