Fig. 4.

CGRP receptor antagonist inhibited phosphorylation of ERK and YAP in OSCC xenograft. a In vivo growth of HSC3 xenograft in nontreated mice and those treated with 20 mg/kg rimegepant, n = 6 mice. (Left panel). Representative HE images of HSC3 xenografts in mice treated with vehicle or 20 mg/kg rimegepant. (Right panel). Scale bar, 1 mm. b Immunostaining of Ki67 in tumor xenograft in nontreated or treated group. Scale bars, 50 μm. c Quantification of Ki67-positive area in tumor xenograft of the nontreated or treated group, n = 15 random fields from 5 mice. d Immunostaining of p-ERK in tumor xenograft of nontreated or treated group. Scale bars, 50 μm. e Quantification of p-ERK-positive area in tumor xenograft of the nontreated or treated group, n = 15 random fields from 5 mice. f Immunostaining of YAP in tumor xenograft of nontreated or treated group. Scale bars, 50 μm. g Quantification of the percentage of YAP nuclear-positive cells of the nontreated or treated group, n = 9 random fields from 3 mice. h Simplified illustration of trigeminal A_2AR mediated CGRP release that activates ERK and YAP in tumor cells. Statistical analysis was conducted using two-way ANOVA with Bonferroni post hoc test (a) and unpaired Student’s t-test (c, e, g)