Human umbilical cord mesenchymal stem cells promote the proliferation of HepG-2 cells through interleukin-6/STAT3 signaling pathway / 中国组织工程研究

ABSTRACT

BACKGROUND:Human umbilical cord mesenchymal stem cel s (hUC-MSCs) can secrete a variety of factors involved in the regulation of tumor proliferation, metastasis and angiogenesis. Probably, interleukin-6 (IL-6) is one of the most important inflammatory factors. OBJECTIVE:To explore the effect of hUC-MSCs on the proliferation and migration of HepG-2 hepatocyte carcinoma cel s via the IL-6/STAT3 signaling pathway. METHODS:IL-6 expression levels in hUC-MSCs and HepG-2 cel s were determined by ELISA. STAT3 and p-STAT3 expression levels were determined by western blot assay. Transcription levels of PCNA, CyclinD1 and STAT3 genes were measured by RT-PCR. HepG-2 cel proliferation was analyzed by flow cytometry and cel counting kit-8 assays. The migration capacity of HepG-2 cel s was evaluated through a scratch test and Transwel assays. RESULTS AND CONCLUSION:The IL-6 level in the hUC-MSCs was significantly higher than that in the HepG-2 cel s (P<0.05). Both the hUC-MSC conditioned culture medium and IL-6 could be used for STAT3 activation. The addition of an IL-6 neutralizing antibody significantly weakened the activation of STAT3 in HepG-2 cel s by the hUC-MSCs-conditioned culture medium. In the presence of the IL-6 neutralizing antibody or the STAT3 inhibitor, AG490, the mRNA expression levels of HepG-2 proliferation-related genes (PCNA, CyclinD1 and Survivin) were significantly reduced. The proliferation and migration capacity of HepG-2 cel s were also significantly decreased by this treatment. Taken together, hUC-MSCs can secrete IL-6 to activate the STAT3 signaling pathway, thereby promoting the proliferation and migration of HepG-2 cel s.