Salmonella typhimurium Mediated Delivery of Apoptin in Human Laryngeal Cancer

Guo-fang Guan¹, Ming Zhao¹, Li-ming Liu², Chun-shun Jin¹, Kai Sun¹, De-jun Zhang¹, Duo-jiao Yu¹, Hong-wei Cao¹, Yan -qing Lu¹, Lian-ji Wen^1✉

1. Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, P. R. China
2. Jilin Academy of Agricultural Science and Technology, Jilin 132101, P. R. China

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Citation:
Guan Gf, Zhao M, Liu Lm, Jin Cs, Sun K, Zhang Dj, Yu Dj, Cao Hw, Lu Yq, Wen Lj. Salmonella typhimurium Mediated Delivery of Apoptin in Human Laryngeal Cancer. Int J Med Sci 2013; 10(12):1639-1648. doi:10.7150/ijms.6960. Available from http://www.medsci.org/v10p1639.htm

Abstract

An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.

Keywords: tumours specifically therapy, attenuated Salmonella typhimurium, laryngeal cancer, Apoptin, apoptosis