birinapant and Liver-Neoplasms

The present study investigated the effects and molecular mechanism of the second mitochondria‑derived activator of caspase (SMAC) mimetic birinapant on the proliferation and apoptotic rate of liver cancer cells. Western blotting and reverse transcription‑quantitative PCR were used to detect the protein and mRNA expression levels of cellular inhibitor of apoptosis 1 (cIAP1) and tumor necrosis factor receptor‑associated factor 3 (TRAF3) in the liver cancer cell lines Huh7, H22 and HepG2, and the hepatocyte line AML12. Annexin V‑FITC and Transwell assays were used to assess the effect of birinapant pretreatment on the apoptotic rate and invasive ability of liver cancer cells. Lentivirus‑mediated silencing of TRAF3 was performed in liver cancer cells. Western blotting was used to detect the lentivirus silencing efficiency. A subcutaneous hepatocellular carcinoma model was established in nude mice and 15 days after tumor induction the subcutaneous tumors were measured in each group. Immunohistochemistry assays were used to detect the protein expression levels of proliferating cell nuclear antigen and caspase‑3. The results suggested that the expression levels of cIAP1 and TRAF3 were lower in Huh7, H22 and HepG2 cells compared with AML12 cells. Pretreatment with birinapant promoted apoptosis and inhibited invasion of liver cancer cells by activating the cIAP1/TRAF3 axis. Birinapant also promoted apoptosis and inhibited the growth of subcutaneous hepatocellular carcinoma tumors in nude mice. The present results suggested that the SMAC mimetic birinapant may promote apoptosis, and inhibit the proliferation and invasion of liver cancer cells. The molecular mechanism responsible for the effects of birinapant may be related to activation of the cIAP1/TRAF3 signaling pathway by birinapant in liver cancer cells.

Topics: Animals; Apoptosis Regulatory Proteins; Biomimetic Materials; Carcinoma, Hepatocellular; Dipeptides; Hep G2 Cells; Humans; Indoles; Inhibitor of Apoptosis Proteins; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondrial Proteins; Neoplasm Proteins; Signal Transduction; TNF Receptor-Associated Factor 3; Xenograft Model Antitumor Assays

To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms.. Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18. Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (. Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.

Topics: Animals; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Dipeptides; Humans; Indoles; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Mitochondrial Proteins