Delivery of the Co-expression Plasmid PEndo-Si-Stat3 by Attenuated Salmonella Serovar Typhimurium for Prostate Cancer Treatment

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2013 Mar 7

PMID 23463096

Citations 10

Authors

Xin Li

Yang Li

Bo Wang

Kun Ji

Zuowen Liang

Baofeng Guo

Jiadi Hu

Di Yin

Yanwei Du

Dennis J Kopecko

Dhananjaya V Kalvakolanu

Xuejian Zhao

Deqi Xu

Ling Zhang

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate the therapeutic utility of an attenuated bacterium carrying a plasmid that co-expresses Endostatin, an inhibitor of tumor neovasculogenesis, and a shRNA that targets Stat3 to suppress prostate cancer growth.

Methods: Plasmid pEndo-Si-Stat3 was constructed and introduced into an attenuated strain of Salmonella enterica serovar typhimurium. The resultant recombinant bacterium was used as a vector to deliver the plasmid to tumor cells growing in vivo. Tumor-associated gene and protein expression changes were measured by using RT-PCR and Western blot analyses. Expression of Endostatin in tumor tissue was detected by ELISA. The presence of vector bacteria in tissues was monitored and tumor destruction was assessed by using TUNEL and H&E staining assays.

Results: Bacterially delivered pEndo-Si-Stat3 decreased Stat3 levels and increased Endostatin expression in mouse tumors, resulting in a significant suppression of tumor growth (P < 0.01). Expression of Bcl-2 and PCNA was down-regulated and Caspase3 expression was up-regulated to promote apoptosis of tumor cells.

Conclusions: Successful delivery by attenuated Salmonella of the combination therapeutic plasmid simultaneously knocked down the expression of Stat3 and resulted in over-expression of Endostatin, which synergistically inhibited prostate cancer growth.

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