Fig. 1: Combined inhibition of Wnt and Sema3C pathways improves survival in a mouse model of GBM.
From: Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma
a Kaplan–Meier curve of GBM model. 14 days after NSG mice were intracranially injected with 387 GSCs, they were treated with either vehicle (n = 16, median survival 27 days) or LGK974 (n = 16, median survival 28 days) 5 mg/kg twice a day for 14 days by oral gavage (Log-rank test p = 0.4973). b Immunoblot of TCF1 expression in GBM tissue of representative control or LGK974 treated animals in (a) (representative 2 samples from each group were shown out of 9 samples analyzed from each group). Sox2 and α-Tubulin were used as loading controls. c Multiple antigen immunohistochemistry staining of TCF1 (red, nucleus) and Sema3C (yellow, cytosol) in human GBM samples (representative pictures from 27 samples were shown). Left: 10x objective view with scale bar 200 μM. Right: 63x oil objective view with scale bar 50 μM. d Scatterplot and linear regression analysis of TCF1 and Sema3C positive stained cells in human GBM (n = 27 GBM samples, simple linear regression test, R2 = 0.66, p < 0.0001, Slope = 0.6034, 95% confidence interval 0.43 to 0.78). e Western blots of TCF1 and Sema3C after knockdown of TCF1, Sema3C, or both in 387 GSCs used in orthotopic xenograft model in figure panels (f) and (g). f Left panels: H&E staining of mouse brain panorama image. Scale bar 2 mm. Right panels: Ki67 immunohistochemistry staining in shNT, shSema3C, shTCF1, or shSema3C plus shTCF1 knockdown tumors. Scale bar 50 μM. Representative images of 387 GSC-derived xenograft tumor samples of euthanized animals (as in C) are shown (one sample from each group out of 14 was shown). g Kaplan–Meier curve of 387 GSC-derived orthotopic xenografts expressing shNT (median survival, 32 days), shSema3C (median survival, 103 days), shTCF1 (median survival, 143 days) or shSema3C + shTCF1 double knockdown (median survival not reached) (n = 14 for each group). Log-Rank test, each group compared with control p < 0.0001; shSema3c vs. shTCF1, P = 0.7461; shSema3C vs. shSema3C + shTCF1, p = 0.0055; shTCF1 vs. shSema3C + shTCF1, p = 0.0035. Source data are provided as a Source data file.
