A pumpkin polysaccharide induces apoptosis by inhibiting the JAK2/STAT3 pathway in human hepatoma HepG2 cells

The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity. In addition, the protein expression of SHP-1 was increased in cells in response to PPPF treatment, whereas SHP-2, SOCS-1 and SCOS-3 protein expression remain unchanged. In vivo animal experiment also indicated that PPPF had a potent inhibitory effect on tumor growth in mice bearing HepG2 xenograft tumors. Thus we can conclude that PPPF directly induces apoptotic cell death of HepG2 cells via down-regulation of the JAK2/STAT3 signal transduction pathways, which may facilitates the development of a therapeutic strategy for treating HCC.