Fig. 1.

Synergistic cytotoxicity was observed from the combination of regorafenib and TMZ. A Green, blue and red frames point out the expression of CXCL-1, CXCL-12, and CXCL-16 on chemokine protein array membrane after 120 μM TMZ treatment for 24 h in U87 cells. B Box plots of CXCR4 mRNA expression level from GBM and LGG patient’s normal (gray) and tumor (pink) samples (*p < 0.05 vs. normal tissue). C Overall survival of glioma patients of either high or low mRNA expression levels of CXCR4 (dot line represented as 95% confidence interval). D The endogens CXCR4 protein expression levels of SVG p12 and four GBM cells. E The viability of U-87 MG and BP-5 after TMZ alone, TMZ combined F–G siCXCR4, H–I w/o AMD3100, J–K w/o CXCR4 recombinant protein, L–M w/o LIT-927, or N–O w/o CXCL12 recombinant protein are displayed. P–Q Western blotting results of CXCR4 and CXCL12 after different treatments are displayed. Relative full blot images are presented in Supplementary Fig. 10. (a¹ p < 0.05, a² p < 0.01 vs. 0 μM TMZ; b¹ p < 0.05, b² p < 0.01 vs. 0 μM AMD3100, 50 ng/ml CXCR4, 0.5 μM LIT-927 or 100 ng/ml CXCL12; c² p < 0.01 vs. U-87 MG cells). Abbreviations: LGG, low grade glioma; GBM, GBM; n, normal; T, tumor; TPM, trans per million; AMD, 30 μM AMD3100; LIT, 0.5 μM LIT-927; + T, plus TMZ