Abstract
The aim of the present study was to investigate the expression of proteins associated with the sustained activation of the signal transducer and activator of transcription (STAT)-3 pathway during diethylnitrosamine (DEN)-induced rat liver carcinogenesis. DEN was intermittently administered to rats to induce liver cancer, and light and electron microscopy were used to observe the morphological changes in the liver during carcinogenesis. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect the expression of STAT-3, phosphorylated (p)-STAT-3, matrix metalloproteinase (MMP)-10, vascular endothelial growth factor (VEGF), kinase insert domain receptor (KDR), hypoxia inducible factor (HIF)-1α, basic fibroblast growth factor (bFGF) and interleukin (IL)-10, in order to investigate the association between STAT-3 and p-STAT-3 expression and MMP-10, VEGF, KDR, HIF-1α, bFGF and IL-10. The western blotting and qPCR results revealed that the expression of STAT-3, p-STAT-3, MMP-10, VEGF, KDR, HIF-1α, bFGF and IL-10 proteins gradually increased during carcinogenesis. Furthermore, the STAT-3 and p-STAT-3 levels were found to positively correlate with MMP-10, VEGF, KDR, HIF-1α, bFGF and IL-10 protein expression. During DEN-induced rat liver carcinogenesis, STAT-3 protein continually activated MMP-10, VEGF, KDR, HIF-1α, bFGF and IL-10, and its expression was found to positively correlate with the expression of these proteins.
Highlights
Tumor invasion and metastasis is a complex process in which tumor cells lose their cell‐cell adhesion, penetrate the basementKey words: signal transducer and activator of transcription‐3, sustained activation, diethylnitrosamine, rats, liver cancer membrane and extracellular matrix (ECM) at the primary site to enter the blood circulation, and evade immune surveillance and migrate to other areas of the body to continue growing [1]
There is continuous signal transducer and activator of transcription (STAT)‐3 activation, resulting in disordered janus tyrosine kinase (JAK)‐STAT signal transduction, which is typical of tumor cells during invasion and metastasis [3]
Jenkins et al [5] found that STAT‐3 deletion mutants completely reversed the splenomegaly, hepatic acute phase reaction, abnormal lymphocyte activation and spontaneous gastric antrum cancer observed in gp130 mutant mice, demonstrating that the sustained activation of STAT‐3 is important for the abnormal proliferation of a variety of cells
Summary
Tumor invasion and metastasis is a complex process in which tumor cells lose their cell‐cell adhesion, penetrate the basement. Elucidating the mechanisms of liver carcinogenesis and progression may contribute to the prevention of this disease and the development of targeted therapy
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