Figure 8

A working model for the synergistic effect of TPL and ATF on tumour cells. TPL and ATF cooperatively induce apoptosis through caspase-dependent pathway and cell cycle arrest. In HCT116 cells, combined treatment with TPL and ATF at a low dosage inhibits AKT phosphorylation and subsequently inactivates NF-κB. The inhibition of NF-κB leads to down-regulation of c-FLIP, activation of caspases-9/caspase-3 and JNK-c-JUN pathway, and cell cycle arrest, which finally promotes cell apoptosis. In addition, the suppression of NF-κB leads to decreased expression of uPAR, MMP-9 and phospho-FAK, thereby inhibiting tumor cell migration and invasion. Furthermore, ATF can segregate uPA from its receptor uPAR, thus blocking ECM remodeling and anti-angiogenesis processes.