Figure 5.

Activation of STAT3 mediated irradiation-inhibited tumor neovasculature through HIF-1α/CXCL12 and HIF-1α/VEGFA signaling pathway. (a) VEGFA and CXCL12 mRNA expression levels in H460 and HCC827 xenograft mice models were assessed by quantitative reverse transcription polymerase chain reaction; GAPDH is used as an internal control. Each bar represents mean ± SD of triplicate samples from a representative experiment (*p < 0.05, p-value was calculated by one-way analysis of variance). (b) p-STAT3, HIF-1α, VEGFA and CXCL12 protein expression levels in H460 and HCC827 xenograft mice models were assessed by western blotting; GAPDH is used as an internal control. S3I-201, a STAT3 inhibitor, was used to examine the effect on downstream signaling in vitro. P-STAT3, HIF-1α, VEGFA and CXCL12 protein expression levels in H460 (c) and HCC827 (d) cells were assessed by western blotting; GAPDH is used as an internal control.

CRT, conventional radiation therapy; d, day; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HFRT, hypo-fractionation radiotherapy; HIF-1, hypoxia inducible factor-1; STAT3, signal transducers and activators of transcription 3; VEGF, vascular endothelial growth factor.