In this study, we have shown that chemically synthesized siRNAs specifically targeting TF successfully knocked down the expression of TF in both protein and mRNA levels

by 80% to 85% in human lung adenocarcinoma cells A549. Then the assays as described above detected the effects on biological behavior of A549 cells in vitro. By the MTT and clonogenic assays, we were able to first show that the proliferation of the TF-siRNA transfected lung adenocarcinoma cells is significantly inhibited in vitro, but previous studies have failed to show that in colorectal cancer cells and B16F10 melanoma cells [11, 12, 31]. Using wound healing and transwell assays, TF-siRNA attenuated the potential of invasion and metastasis in lung adenocarcinoma cells. Furthermore, flow cytometric analysis revealed that knockdown of TF expression induced apoptosis in A549 cells. According to Liproxstatin-1 these results, we believed that besides participating in angiogenesis, TF also plays a key role in cell proliferation and metastasis of lung adenocarcinoma. After binding of FVIIa, the TF forms

a high affinity complex with FVIIa or FVIIa-FXa, and other than initiating the coagulation cascade, the complex induce signal transduction by binding to a family of transmembrane domain G protein-coupled AL3818 ic50 cell surface receptors called protease-activated receptors (PARs), specially, PAR-1/-2 [32], which are expressed by numerous tumor cells and tissues [33, 34]. In the tumor, it has recently emerged as important players in growth and metastasis, but previous studies have lacked information about the downstream signal pathways induced by

the inhibition of the TF expression via TF-siRNA in lung cancer cells. In the current study, we established PIK3C2G that down-regulation of TF expression in lung adenocarcinoma cells suppressed the Erk1/2 MAPK and PI3K/Akt signal pathways, which are well recognized for mediating cell proliferation and apoptosis [35, 36]. Therefore, the result explains, at least in part, why TF-siRNA inhibited the cell proliferation and induced the apoptosis in A549 cells. Furthermore, the expressions of MMP-2/-9 also were down-regulated in TF-siRNA transfected cells, and it may suggest that MMP-2/-9 are the downstream products of the TF complex induced cell signaling. MMPs are a family of enzymes that degrade proteins in tissue extracellular matrices, which are clearly involved in cancer progression, including tumor cell degradation of basement membranes and stroma and blood vessel penetration [27]. Consequently, the reduction of MMP-2/-9 by TF-siRNA exactly results in attenuating the metastatic potency of lung adenocarcinoma cells. Besides experiments in vitro that give new insights into the antitumor effects of TF-siRNA in lung adenocarcinoma, we used a nude mouse eFT508 xenograft model of lung adenocarcinoma to better evaluate the TF-siRNA effects in vivo.