Carboxyl Esterase-TRAIL Expressing Human Adipose Stem Cells Inhibit Tumor Growth in Castration-Resistant Prostate Cancer-Bearing Mice with Less Toxicity.

Abstract

It has been proposed that CRPC treatment with reduced systemic toxicity can be achieved by employing genes that express enzymes that activate pharmacological agents. In this paper, we report our study that used human adipose-derived stem cells (ADSC), rabbit CE, and human TRAIL with reduced toxicity to explore how tumor development can be suppressed in CRPC-bearing mouse models. In vitro and in vivo directional migration of ADSC.CE.sTRAIL cells toward PC3 cells was significantly stimulated.ADSC.CE.sTRAIL showed higher suicide effects than did ADSC, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. PC3 cells co-cultured with ADSC.CE.TRAIL showed higher cytotoxicity than did CPT-11 monotherapy, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. ADSC.CE.sTRAIL showed higher apoptosis than did CPT-11 monotherapy, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. In the in vivo study, ADSC.CE.sTRAIL inhibited tumor growth more than did CPT-11 monotherapy, ADSC.CE, or ADSC.sTRAIL under CPT-11 treatment. The evidence suggests that patients’ own ADSC could be used in clinical trials for CRPC treatment based on therapeutic stem cells that express CE and TRAIL complex genes.