Effects of JAK2/STAT3 signaling pathway on angiogenesis in non-small cell lung cancer

Abstract

To investigate the relationship between janus kinase2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway and angiogenesis in non-small cell lung cancer (NSCLC) and explore the effects on the mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) by blocking JAK2/STAT3 signaling pathway. Immunohistochemistry was used to determine the expression of P-JAK2, P-STAT3 and microvessel density (MVD) in 68 NSCLC tissues and 27 normal lung tissues. And the relationship with their clinical pathological features was analyzed. Human lung cancer A549 cells were treated with different concentrations of AG490. Cell proliferation was measured by MTT assay. Western blot was performed to detect the activation of JAK2/STAT3 signaling pathway. The mRNA expressions of VEGF and bFGF were determined by RT-PCR (reverse transcription-polymerase chain reaction). A549 cells were transfected with STAT3 siRNA. And the protein of STAT3, Phos-STAT3 (P-STAT3) and mRNA levels of VEGF and bFGF were detected. The activation of JAK2/STAT3 signaling pathway was closely related to MVD in NSCLC. AG490 and STAT3 siRNA could block the JAK2/STAT3 signaling pathway and down-regulated the mRNA expressions of VEGF and bFGF in lung cancer cells. JAK2/STAT3 signaling pathway plays an important role in the angiogenesis of NSCLC. Blocking this pathway may inhibit the expression of angiogenic cytokines. JAK2/STAT3 signaling pathway may be a critical therapeutic target for the treatment of angiogenesis in NSCLC.