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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 755 - 762 (8page)
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Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.
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참고문헌 (26)
참고문헌 신청
Adriana, N. / 2018 / Anti-proliferative, proapoptotic and anti-oxidative activity of Lactobacillus and Bifidobacterium strains : A review of mechanisms and therapeutic perspectives / Crit. Rev. Food Sci. Nutr 16:1~12
Cousin, F. J. / 2016 / The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-base therapy in colorectalcancer / Oncotarget 7:7161~7178
Dantoft, S. H. / 2013 / Complete genome sequence of Pediococcus pentosaceus strain SL4 / Genome Announc 1:e01106~e01113
Drouault, S. / 1999 / Survival, physiology, and lysis of Lactococcus lactis in the digestive tract / Appl. Environ. Microbiol 65:4881~4886
Flambard, B. / 2000 / The autoproteolysis of Lactococcus lactis lactocepin III affects its specificity towards beta-casein / Appl. Environ. Microbiol 66:5134~5140
Cousin, F. J. / 2016 / The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-base therapy in colorectalcancer / Oncotarget 7:7161~7178
Dantoft, S. H. / 2013 / Complete genome sequence of Pediococcus pentosaceus strain SL4 / Genome Announc 1:e01106~e01113
Drouault, S. / 1999 / Survival, physiology, and lysis of Lactococcus lactis in the digestive tract / Appl. Environ. Microbiol 65:4881~4886
Flambard, B. / 2000 / The autoproteolysis of Lactococcus lactis lactocepin III affects its specificity towards beta-casein / Appl. Environ. Microbiol 66:5134~5140
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