Smac mimetic promotes TNF-α to induce apoptosis of gallbladder carcinoma cells.

摘要: Gallbladder carcinoma has a high degree of malignancy. No effective treatment exists for patients with advanced tumors. The second mitochondria-derived activator caspases (Smac) is the antagonist inhibitors apoptosis protein. Smac mimetics are class tumor-targeted drugs undergoing clinical trials. However, studies on effect gallbladder cancer unavailable. In this study, can promote tumor necrosis factor-α (TNF-α) to inhibit proliferation cells and activate apoptotic pathway, thereby promoting ubiquitination Lys48 Receptor interacting protein kinase-1 (RIPK1) leading proteasomal degradation that causes damage RIPK1 integrity. formation complex I (RIPK1, factor 1-associated death domain protein, TNF receptor-associated 2) inhibited. Then, nonubiquitinated binds Fas-associated caspase-8 form II promotes receptor pathway apoptosis. Animal experiments further verify TNF-α combined growth transplanted tumors induce cells. This research provides new direction targeted therapy cancer.