Fig. 6. In vivo significance of co-targeting STAT3 and AKT to suppress HIF-1α signaling and to increase drug sensitivity.

A A proposed model of xenograft experiment. In brief, six million MDA-MB-231 cells were implanted subcutaneously into the flanks of Balb/c nude mice. Dosing of the indicated drugs was initiated when tumor sizes reached 200 mm³ after 2 weeks. B Primary tumor size was measured (left) and quantified (right). C Primary tumor and representative metastasis specimens (yellow arrow heads) were HE stained (left). The numbers of metastatic lesions in lung and liver were quantified (right). D Expressions of HIF-1α and its target genes from inoculated tumor tissue were detected via qRT-PCR. E Western blotting illustrated the inhibition of STAT3 or PI3K/AKT signaling by its corresponding inhibitor as well as the downregulations of HIF-1α and its target genes. Error bars represent means ± SD from triplicates. Data are representative of at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001; ns, not significant.