Tumor necrosis factor-related apoptosis-inducing ligand modulates angiogenesis and apoptosis to inhibit non-small cell lung carcinoma tumor growth in mice.

Abstract

ObjectiveTo investigate the anti-tumor effect and mechanism of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in non-small cell lung carcinoma (NSCLC) in mice.MethodsWe first established NSCLC animal models using 20 BALB/c nude mice that were randomly divided into two equal groups (n = 10): TRAIL-treated and control untreated groups. We measured expression levels of B cell leukemia/lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), vascular endothelial growth factor (VEGF), and VEGF receptor (VEGFR). We also performed microvessel density, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunohistochemical assays to determine the effect of TRAIL on apoptosis and angiogenesis in NSCLC tumors in vitro.ResultsTRAIL inhibited tumor growth in the NSCLC mouse model, and the TUNEL assay showed that it induced tumor cell apoptosis. Immunohistochemical staining revealed that TRAIL induced Bcl-2 protein downregulation, suggesting that the mitochondrial apoptotic pathway is involved in regulating NSCLC apoptosis. However, TRAIL did not affect Bax protein expression. Immunohistochemical staining also revealed significantly reduced VEGF and VEGFR protein expression in the TRAIL group, indicating that TRAIL limits angiogenesis in NSCLC tumor tissues.ConclusionsIn conclusion, TRAIL inhibits NSCLC growth both by inducing tumor cell apoptosis and restricting angiogenesis in tumors.