Therapeutic Effect of Recombinant Salmonella VNP20009-M on Osteosarcoma

Abstract

Objective To investigate the therapeutic effect of attenuated salmonella VNP20009-M that carries a methioninase gene on osteosarcoma. Methods Recombinant salmonella VNP20009-M was co-cultured with a human osteosarcoma cell line. After the methioninase gene was overexpressed in osteosarcoma cells, cell proliferation, migration and apoptosis were detected. Finally, we evaluated the effect of the attenuated salmonella VNP20009-M on the subcutaneous xenograft in the nude mice by intratumorally injecting different dosages of VNP20009-M. Results It was verified by plasmid PCR that the methioninase gene was only found in the target strain VNP20009-M and had high methioninase activity. The recombinant salmonella was successfully constructed. VNP20009-M significantly induced the apoptosis of MNNG-HOS cells. Overexpression of the L-methioninase gene in the osteosarcoma cells significantly inhibited cell proliferation and migration, compared with the control group. The body weight of the subcutaneous tumor-bearing mice after VNP20009-M treatment did not change significantly, and tumor growth was significantly retarded. Conclusion VNP20009-M could induce the apoptosis and inhibit the proliferation and migration of osteosarcoma cancer cells, and can be a novel and highly effective drug candidate for osteosarcoma in the clinic.

Keywords

• salmonella
• genetic engineering
• methioninase
• osteosarcoma