Combining Nelfinavir With Chloroquine InhibitsIn VivoGrowth of Human Lung Cancer Xenograft Tumors

Abstract

Nelfinavir is a human immunodeficiency virus protease inhibitor that is currently being repositioned as an anticancer drug. Chloroquine, an anti-malarial lysosomotropic drug, inhibits autophagy. It has been reported that the combination of nelfinavir and chloroquine significantly enhances endoplasmic reticulum (ER) stress and induces selective cell death in multiple cell line models (in vitro). We assessed the effects of the combination of these drugs on human NSCLC cell lines in vitro using cell proliferation assay and performed preclinical treatment studies using cell line-derived xenograft mouse models in vivo. In vitro, this combination enhanced inhibition of NSCLC cell proliferation with increased proteotoxicity, including ER stress, and apoptosis. In vivo, the growth of human NSCLC xenograft tumors was inhibited, which correlated with increased apoptosis and induction of ER stress as well as NSCLC growth in vitro. Our findings suggest that the induction of proteotoxicity provides a promising new target for developing anticancer drugs.