Attenuated Salmonella carrying plasmid co-expressing HPV16 L1 and siRNA-E6 for cervical cancer therapy

Abstract

Human papillomavirus (HPV) infection is the major etiological factor for cervical cancer. HPV prophylactic vaccines based on L1 virus-like particles have been considered as an effective prevention method. However, existing recombination vaccines are too expensive for developing countries. DNA vaccines might be a lower-cost and effective alternative. In this study, a plasmid (pcDNA3.1-HPV16-L1) and a co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) carried by attenuated Salmonella were constructed and their prevention and treatment effect on cervical cancer were observed, respectively. The results showed that pcDNA3.1-HPV16-L1 carried by attenuated Salmonella could induce the production of HPV16-L1 antibodies, IL-2 and INF-γ in mice serum, which presented its prevention effect on HPV. Subsequently, E6 and E7 gene silencing by pCG-siE6 inhibited the growth of cervical cancer both in vitro and in vivo. Furthermore, L1 up-regulation and E6/E7 down-regulation caused by co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) contributed to a significant anti-tumor effect on the mice. This study suggests that pcDNA3.1-HPV16-L1-siE6 carried by attenuated Salmonella has a synergistic effect of immune regulation and RNA interference in cervical cancer treatment.