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携带共表达 HPV16 L1 和 siRNA-E6 质粒的减毒沙门氏菌用于宫颈癌治疗。

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

机构信息

Department of Rehabilitation, School of Nursing, Jilin University, 965 Xinjiang Street, Changchun, China.

Department of Gynecology, Second Hospital, Jilin University, Changchun, China.

出版信息

Sci Rep. 2021 Oct 11;11(1):20083. doi: 10.1038/s41598-021-99425-3.

DOI:10.1038/s41598-021-99425-3
PMID:34635698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8505555/
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.

摘要

人乳头瘤病毒（HPV）感染是宫颈癌的主要病因。基于 L1 病毒样颗粒的 HPV 预防性疫苗已被认为是一种有效的预防方法。然而，现有的重组疫苗对于发展中国家来说过于昂贵。DNA 疫苗可能是一种成本更低、更有效的替代方法。在本研究中，构建了携带减毒沙门氏菌的质粒（pcDNA3.1-HPV16-L1）和共表达质粒（pcDNA3.1-HPV16-L1-siE6），并分别观察了它们对宫颈癌的预防和治疗效果。结果表明，携带减毒沙门氏菌的 pcDNA3.1-HPV16-L1 能够诱导小鼠血清中 HPV16-L1 抗体、IL-2 和 INF-γ的产生，表现出对 HPV 的预防作用。随后，pCG-siE6 对 E6 和 E7 基因的沉默抑制了宫颈癌在体外和体内的生长。此外，共表达质粒（pcDNA3.1-HPV16-L1-siE6）引起的 L1 上调和 E6/E7 下调有助于对小鼠产生显著的抗肿瘤作用。本研究表明，携带减毒沙门氏菌的 pcDNA3.1-HPV16-L1-siE6 在宫颈癌治疗中具有免疫调节和 RNA 干扰的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/8b5b89845259/41598_2021_99425_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/11afad264966/41598_2021_99425_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/cd214081b774/41598_2021_99425_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/05e5f912e434/41598_2021_99425_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/e3ac7b8527c6/41598_2021_99425_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/115b21ccec36/41598_2021_99425_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/31f4c693690a/41598_2021_99425_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/8b5b89845259/41598_2021_99425_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/11afad264966/41598_2021_99425_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/cd214081b774/41598_2021_99425_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/05e5f912e434/41598_2021_99425_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/e3ac7b8527c6/41598_2021_99425_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/115b21ccec36/41598_2021_99425_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/31f4c693690a/41598_2021_99425_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a085/8505555/8b5b89845259/41598_2021_99425_Fig7_HTML.jpg

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