Fig. 7

BMP2 enhances angiogenesis in vivo in HCC through MAPK/p38 signaling pathway activation. The MARK/p38 signaling pathway was inhibited by SB-239063 when BMP2 was over-expressed to identify the functional significance of MARK/p38 signaling pathway activation in the effects of BMP2 on tumor angiogenesis. a Tumor volume and weight of nude mice. b Representative images of xenograft tumors. c HE staining analysis of pathological changes in tumor tissues (× 400). d Angiogenesis in tumor tissues under a laser confocal microscope (× 400). e VEGF expression patterns in the serum of nude mice detected by ELISA. f Immunohistochemical staining for CD31 (× 400) showing MVD value. g Cell apoptosis detected by TUNEL (× 400). h Positive expression of Caspase-3 and PCNA examined by immunohistochemistry (× 400). i Western blot analysis of VEGF, VEGF-C, MMP-2, MMP-9, Vimentin, and E-cadherin protein patterns. n = 6. Data were expressed by mean ± standard deviation. p values were obtained using the Mann-Whitney U test. *p < 0.05; HCC, hepatocellular carcinoma; MAPK, mitogen-activated protein kinase; NC, negative control; VEGF, vascular endothelial growth factor; PCNA, proliferating cell nuclear antigen; ELISA, enzyme-linked immunosorbent assay; HE, hematoxylin-eosin; MVD, microvessel density; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling