Tumor necrosis factor-related apoptosis-inducing ligand additive with Iodine-131 of inhibits non-small cell lung cancer cells through promoting apoptosis.

Abstract

Non-small-cell lung cancer (NSCLC) accounts for ~80% of human lung cancer cases and is the most common cause of cancer-associated mortality worldwide. Reports have indicated that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Iodine-131 (I-131) can induce tumor cell apoptosis. The purpose of the present study was to investigate the additive efficacy of TRAIL and I-131 on NSCLC cells. The present study demonstrated that additive treatment of TRAIL and I-131 (TRAIL-I-131) significantly inhibited the growth and aggressiveness of NSCLC cells compared with single TRAIL or I-131 treatment. Results demonstrated that TRAIL-I-131 treatment induced apoptosis of NSCLC cells, with western blot analysis confirming that TRAIL-I-131 treatment increased proapoptotic Bad and Bax expression levels, while antiapoptotic Bcl-2 and Bcl-w protein levels were decreased in NSCLC cells. The present study demonstrated that TRAIL-I-131 treatment inhibited vascular endothelial growth factor (VEGF) and activator protein-1 (AP-1) in NSCLC cells. Potential mechanism analyses identified that TRAIL-I-131 treatment induced apoptosis of NSCLC cells through caspase-9 activation. In vivo assays revealed that TRAIL-I-131 treatment significantly inhibited NSCLC tumor growth and increased apoptotic bodies in tumor tissues. Immunohistology demonstrated that caspase-9 was upregulated and VEGF was downregulated in tumor tissues in TRAIL-I-131-treated tumors. In conclusion, these results indicate that TRAIL combined with I-131 promoted apoptosis of NSCLC through caspase-9 activation, which may be a promising anticancer therapeutic schedule for the treatment of NSCLC.