An increasing number of studies have implicated Stat protein activation, particularly Stat3, in transformation and tumor progression[4]. Activated Stat3 has been shown to promote cell proliferation, metastasis, and angiogenesis, as well as protect tumor cells from apoptosis by regulating associated genes, such as Bcl-xL, Mcl-1, Bcl-2, Fas, cyclin D1, survivin, c-Myc, VEGF, MMP-2, and MMP-9[5–7]. Recently, accumulating evidence has

indicated that abnormalities in the Stat3 pathway are involved in the oncogenesis of several cancers. For example, Scholz [8] and coworkers reported that activation of the Stat3 Fosbretabulin signaling pathway plays an important role in the progression of pancreatic cancer, and constitutive activation of Stat3 correlates with cell proliferation in stomach adenocarcinoma[9], prostate cancer[10], breast carcinoma[11], and non-small cell lung cancer[12] and also inhibits apoptosis[13, LGX818 cell line 14]. Conversely, inhibition of the Stat pathway suppresses cancer cell growth and invasion and induces CCI-779 price apoptosis in various cancers[8, 11, 15, 16]. Jak is responsible for the tyrosine phosphorylation of Stat3 in response to extracellular signals and oncogenes. The newly described Jak inhibitor AG490 blocks the constitutive activation of Stat3[17]. AG490 was used to selectively

block the Jak/Stat3 signaling pathway and inhibit activation of Stat3 in colorectal cancer cells[18]. The pleiotropic cytokine interleukin-6 (IL-6) is a major activator of Stat3; IL-6 stimulates the formation of tyrosine-phosphorylated Stat3 (p-Stat3) in cancer cells[19, 20]. Through the Jak/Stat3 signaling pathway, IL-6 plays an important role in cell proliferation, apoptosis, metastasis, and other biological activities [21]. In the present study, we used AG490 to deplete Stat3 protein in the human pancreatic cancer cell line SW1990 and IL-6 to activate Stat3 protein in the human pancreatic cancer cell line Capan-2; we then investigated the changes in cell proliferation and invasion.

We also examined the expression Methocarbamol of Stat3 and its active phosphorylated form in human pancreatic cancer cell lines. In addition, we evaluated the changes in matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) mRNA and protein expression. Our aim was to demonstrate that the Stat3 signaling pathway may be critical for the invasive behavior of pancreatic tumors. Inhibition of this pathway may offer a novel strategy for pancreatic cancer treatment. Methods Cells and reagents The human pancreatic cancer cell lines SW1990 and Capan-2 were obtained from the American Type Culture Collection. Tumor cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM), supplemented with 10% fetal calf serum, 100 units/ml penicillin and 100 μg/mL streptomycin, in a humidified incubator with an atmosphere of 5% CO2 and 95% air at 37°C.