p53 gene delivery via a recombinant Salmonella enterica Typhimurium leads to human bladder carcinoma cell death in vitro

Abstract

Numerous studies have attempted to restore the function of the tumour suppressor p53 as an anticancer strategy through gene delivery. However, most studies employed non-bacterial vectors to deliver p53. Various facultative and obligate anaerobic bacteria have been proposed as vectors because of their intrinsic tumour targeting ability and antitumour activity. Salmonella enterica Typhimurium is the most studied bacterial vector in anticancer therapy. We used the previously designed χ11218 strain of S. enterica Typhimurium, displaying regulated delayed lysis, as a vector for delivering p53 to human bladder carcinoma cells, restoring wild-type p53 protein function. We cloned p53 into pYA4545 (containing a eukaryotic expression system) to generate the χ11218 pYA4545p53 strain. Cloning of p53 did not affect the growth or interfere with the invasive and replicative capacity of χ11218 bacteria in tumour cells. Human bladder carcinoma cells (expressing mutated p53) transfected with pYA4545p53 showed a significant increase in the expression of p53 protein. We demonstrated that p53 supplied by χ11218 significantly decreased the viability of human bladder cancer cells in a dose-dependent manner. This study demonstrates the applicability of the attenuated χ11218 strain as a vector for DNA plasmids expressing tumour suppressor genes.