Fig. 8

Therapeutic potential of sulfarotene on HCC PDX tumors with high expression of SOS2. a Representative HE images of sections of human HCC tumor foci with high and low expression levels of SOS2. b-c Comparative statistic analyses of the volumes and weights of tumor nodes derived from human HCC PDXs with high and low expression levels for SOS2. d Differential responses of human HCC PDX tumors with high and low SOS2 expression levels to sulfarotene treatment. PDX tumors from NOG mice (nonobese diabetic mice with severe combined immunodeficiency) with high (CPS > 4) or low (CPS ≤ 4) expression levels of SOS2 were reconstituted and re-transplanted subcutaneously into the flanks of athymic nude mice and subjected to treatment with sulfarotene at 0.22 and 2.2 mg/kg via i.v. injection once every two days for 3 weeks. Representative PDX-derived tumor node images are presented. e-f Statistic analyses of tumor volumes and weights derived from human HCC PDX tumors in (D) (n = 6). g-h Suppression of SOS2, RAS-associated pathways and the proliferation marker Ki67 and elevation of apoptosis marker Caspase-3 by sulfarotene treatment in HCC PDX tumors of high SOS2 expressors. Representative IHC images of sections (g) and statistical analysis of IHC levels of pERK1/2, pAKT, Ki67 and Caspase-3 (h) in HCC PDX tumors with high expression of SOS2 (n = 6). Data are presented as the mean ± SD of 3 independent experiments. **P < 0.01, ***P < 0.001. ns, not significant