Abstract
BackgroundSignal Transducer and Activator of Transcription 3 (STAT3) is an oncogene, which promotes cell survival, proliferation, motility and progression in cancer cells. Targeting STAT3 signaling may lead to the development of novel therapeutic approaches for human cancers. Here, we examined the effects of epigallocathechin gallate (EGCG) on STAT3 signaling in pancreatic cancer cells, and assessed the therapeutic potential of EGCG with gemcitabine or JAK3 inhibitor CP690550 (Tasocitinib) for the treatment and/or prevention of pancreatic cancer.Methodology/Principal FindingsCell viability and apoptosis were measured by XTT assay and TUNEL staining, respectively. Gene and protein expressions were measured by qRT-PCR and Western blot analysis, respectively. The results revealed that EGCG inhibited the expression of phospho and total JAK3 and STAT3, STAT3 transcription and activation, and the expression of STAT3-regulated genes, resulting in the inhibition of cell motility, migration and invasion, and the induction of caspase-3 and PARP cleavage. The inhibition of STAT3 enhanced the inhibitory effects of EGCG on cell motility and viability. Additionally, gemcitabine and CP690550 alone inhibited STAT3 target genes and synergized with EGCG to inhibit cell viability and induce apoptosis in pancreatic cancer cells.Conclusions/SignificanceOverall, these results suggest that EGCG suppresses the growth, invasion and migration of pancreatic cancer cells, and induces apoptosis by interfering with the STAT3 signaling pathway. Moreover, EGCG further enhanced the therapeutic potential of gemcitabine and CP690550 against pancreatic cancer.
Highlights
Signal transduction and activators of transcription (STAT) proteins is a family of cytoplasmic transcription factors which are initially present in inactive forms [1,2]
Conclusions/Significance: Overall, these results suggest that epigallocathechin gallate (EGCG) suppresses the growth, invasion and migration of pancreatic cancer cells, and induces apoptosis by interfering with the Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway
We examined the effects of EGCG on STAT3 signaling in human pancreatic cancer cells, and assessed the interactive effects of EGCG with gemcitabine or JAK3 inhibitor CP690550 on their therapeutic potential
Summary
Signal transduction and activators of transcription (STAT) proteins is a family of cytoplasmic transcription factors which are initially present in inactive forms [1,2]. They are stimulated by the binding of signaling peptides, such as cytokine, growth factors, and hormone, which results in dimerization of their cognate receptors and activation of tyrosine kinases such as Janus kinase (JAK). Among all the STAT family members, STAT3 is the most intimately linked to cell survival and proliferation and tumorigenesis [3,4] It is widely expressed in most tissues and is considered as a potential oncogene. We examined the effects of epigallocathechin gallate (EGCG) on STAT3 signaling in pancreatic cancer cells, and assessed the therapeutic potential of EGCG with gemcitabine or JAK3 inhibitor CP690550 (Tasocitinib) for the treatment and/or prevention of pancreatic cancer
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