Effects of Birinapant on Proliferation and Invasion of MGC-803 Gastric Cancer Cells and Mechanism Underlying These Effects.

Abstract

We studied the effects of birinapant, a mimetic of the second mitochondria-derived activator of caspase (SMAC), on invasion and proliferation of MGC-803 gastric cancer cells and the molecular mechanisms underlying these processes. The expression of cellular inhibitor of apoptosis 1 (cIAP1) and TNF receptor-associated factor 3 (TRAF3) in gastric cancer cell line MGC-803 and normal gastric mucosa GES-1 cells were analyzed by Western blotting and cell immunofluorescence assay. After pretreatment of MGC-803 cells with birinapant, a Transwell invasion assay was used to evaluate the cell invasion ability. MGC-803 cells were implanted under the skin of BALB/c nude mice. The tumors were removed 10 days later and its size was measured. Protein expression of proliferating cell nuclear antigen (PCNA) in the subcutaneous tumors was analyzed by immunohistochemical method. In addition, the expression of cIAP1, TRAF3, pNF-κB, and NF-κB in control and birinapant-treated cells was compared by Western blotting and the rate of cell apoptosis was evaluated by flow cytometry. In untreated MGC-803 gastric cancer cells, the expression of cIAP1 was higher and the expression of TRAF3 was lower than in normal gastric mucosa cell line GES-1. Pretreatment with birinapant inhibited the invasion and proliferation of MGC-803 cells and promoted cell apoptosis. Birinapant also promoted the expression of TRAF3 and inhibited the expression of cIAP1 and pNF-κB in MGC-803 cells. Thus, birinapant inhibited the expression of cIAP1, prevented degradation of TRAF3, and suppressed invasion and proliferation of MGC-803 cells by promoting cell apoptosis.