Fig. 6
Macitentan inhibits metastases sensitizing to platinum. a Patient-derived xenografts (PDX), obtained transplanted subcutaneously PMOV10 cells in nude mice, were treated with vehicle (CTR) or MAC (30 mg/Kg/day, oral daily), CIS (8 mg/kg/i.p. once a week) in mono-therapy or with MAC + CIS combination therapy (upper, treatment scheduling). The comparison of tumor growth levels by two-way ANOVA with group-by-time interaction was statistically significant (p < 0.05). Bars are means ± SD of ten mice for group. Left. Representative tumors of PMOV10 PDX. b The binding of β-arr1, YAP, TEAD, and p53 to ANKRD1 and ET-1 promoter regions was analysed in PDX tumors treated or not with MAC by ChIP assays followed by PCR. c pYAP (S127) and YAP protein expression was evaluated by IB analysis in PDX tumors of PMOV10 treated with MAC and/or CIS and MAC + CIS. Tubulin was used as loading control. d, f Nude mice intraperitoneally (ip) injected with PMOV10 (d) or OVCAR-3 (f) cells and treated as in a (upper, treatment scheduling). Bars are means ± SD of ten mice for group. (*p < 0.001 vs CTR; **p < 0.01 vs MAC or CIS). At the end of the treatment ip organs were examined for tumor nodules. Right, representative ip nodules of PMOV10 PDX and OVCAR-3 xenografts were indicated by white dotted-line circles. e, g pYAP (S127) and YAP protein expression of PMOV10 PDX ip nodules extracts (e) or pYAP, YAP, β-arr1, and p53 protein expression was evaluated by IB analysis of ip nodules extracts of OVCAR-3 xenografts (g) treated with MAC and/or CIS and MAC + CIS. Tubulin was used as loading control
