Abstract
Lactic acid bacteria are known to have beneficial effects on the host, such as preventing carcinogenesis. The present study was designed to evaluate the chemopreventive effects of Lactobacttlus rhamnosus strain GG (LGG) in suppressing bladder cancer formation in a murine subcutaneous model of bladder cancer involving the inoculation of MB49 cells in C57B/L6 mice. After tumor implantation, one group of mice (n=8) was fed LGG immediately. The remaining mice that had tumors between 0.03–0.1 cm3 were divided into two groups: those fed LGG after 7 days (n=7) and those fed saline (n=7). A second group of mice without any inoculation of MB49 cells was fed either LGG (n=10) or saline (n=10) and served as non‐tumor‐bearing controls. LGG was administered orally at 1.6×l08 colony‐forming units daily. Mice fed LGG immediately after tumor cell implantation formed smaller tumors and some did not develop tumors (2 out of 8 mice), when the tumor burden was small. The level of spleen CD3, CD4 and CD8a T lymphocytes, as well as natural killer cells in mice fed immediately with LGG was also higher than that in control tumor‐bearing mice. There was an increase in lymphocytes and granulocytes in tumor sections, especially from the immediately fed group as compared to the controls. Our results suggest that oral consumption of LGG may prevent tumor growth via modulation of the immune system. The potential of LGG as an adjunct therapy in the treatment of bladder cancer could be further explored.
Keywords: Lactobacillus rhamnosus strain GG, Bladder carcinogenesis, MB49 cell line, Immunomodulation
Full Text
The Full Text of this article is available as a PDF (1.8 MB).
REFERENCES
- 1. ) Naeyo , U. O. and Lamm , D. L.Therapy of superficial bladder cancer . Semin. Oncol , 23 , 598 – 604 ( 1996. ). [PubMed] [Google Scholar]
- 2. ) Brosman , S. A.Bacillus Calmette‐Guerin immunotherapy: techniques and results . Urol. Clin. North Am. , 19 , 557 – 564 ( 1992. ). [PubMed] [Google Scholar]
- 3. ) Zhang , Y. , Khoo , H. E. and Esuvaranathan , K.Effects of Bacillus Calmette‐Guerin and interferon α‐2B on cytokine production in human bladder cancer cell lines . J. Urol. , 161 , 977 – 983 ( 1999. ). [PubMed] [Google Scholar]
- 4. ) Lee , Y. K. and Salminen , S.The coming of age of probiotics . Trends Food Sci. TechnoL , 6 , 241 – 245 ( 1995. ). [Google Scholar]
- 5. ) De Roos , N. M. and Katan , M. B.Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998 . Am. J. Clin. Nu.tr. , 71 , 405 – 411 ( 2000. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Aso , Y. , Akaza , H. , Kotake , T. , Tsukamoto , T. , Imai , K. and Naito , S.Preventive effect of a Lactobacillus caseipreparation on the recurrence of superficial bladder cancer in a double blind clinical trial . Eur. Urol. , 27 , 104 – 109 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Asano , M. , Karasawa , E. and Takayama , T.Antitumor activity of Lactobacillus casei (LC 9018) against experimental mouse bladder tumor (MBT‐2) . J. Urol. , 136 , 719 – 721 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Isolauri , E. , Juntunen , M. , Rautanen , T. , Sillanauki , P. and Koivula , T.A human Lactobacillus strain (Lactobacillus casei sp. strain GG) promotes recovery from acute diarrhea in children . Pediatrics , 88 , 90 – 97 ( 1991. ). [PubMed] [Google Scholar]
- 9. ) Biller , J. A. , Katz , P. J. , Flores , A. F. , Buie , T. M. and Gorbach , S. L.Treatment of recurrent Clostridium difficilecolitis with Lactobacillus GG . J. Pediatr. Gastroenterol. Nutr. , 21 , 224 – 226 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Goldin , B. R. , Gualtieri , L. J. and Moore , R. P.The effect of Lactobacillus GG on the initiation and promotion of DMH‐induced intestinal tumors in the rat . Nutr. Cancer , 25 , 197 – 204 ( 1996. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Greene , J. D. and Klaenhammer , T. R.Factors involved in adherence of Lactobacillus to human Caco‐2 cells . Appl. Environ. Microbiol. , 60 , 4487 – 4494 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Gan , Y. H. , Zhang , Y. , Khoo , H. E. and Esuvaranathan , K.Antitumour immunity of Bacillus Calmette‐Guerin and interferon alpha in murine bladder cancer . Eur. J. Cancer , 35 , 1123 – 1129 ( 1999. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Lee , Y. K. , Soh , B. S. and Wu , J. H.Quantitative assessment of phagocytic activity of hemocytes in the prawn, Penaeus merguiensis, by flow cytometric analysis . Cytometry , 43 , 82 – 85 ( 2001. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Kato , I , Ohwaki , M. , Yokokura , T. and Mutai , M.Hostmediated antitumor activity of Lactobacillus casei in mice . Gann , 75 , 72 – 80 ( 1984. ). [PubMed] [Google Scholar]
- 15. ) Perdigon , G. , Alvarez , S. , Rachid , M. , Aguero , G. and Gobbato , N.Symposium: probiotic bacteria for humans, clinical systems for evaluation of effectiveness . J. Dairy Sci. , 78 , 1597 – 1606 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Matsuzaki , T. and Chin , J.Modulating immune responses with probiotic bacteria . Immunol. Cell Biol. , 78 , 67 – 73 ( 2000. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Sawamura , A. , Yamaguchi , Y. , Toge , T. , Nagata , N. , Ikeda , H. , Nakanishi , K. and Asakura , A.Enhancement of immuno‐activities by oral administration of Lactobacillus casei in colorectal cancer patients . Biotherapy , 8 , 1567 – 1572 ( 1994. ). [Google Scholar]
- 18. ) Takagi , A. , Matsuzaki , T. , Sato , M. , Nomoto , K. , Morotomi , M. and Yokokura , T.Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism . Carcinogenesis , 22 , 599 – 605 ( 2001. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Matsuzaki , T.Immunomodulation by treatment with Lactobacillus casei strain Shirota . Int. J. Food Microbiol. , 41 , 133 – 140 ( 1998. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Perdigon , G. , De Macias , M. E. , Alvarez , S. , Oliver , G. and De Ruiz Holgado , A. P.Systemic augmentation of the immune response in mice by feeding fermented milks with Lactobacillus casei and Lactobacillus acidophilus . Immunology , 63 , 17 – 23 ( 1988. ). [PMC free article] [PubMed] [Google Scholar]
- 21. ) Brandtzaeg , P. , Baklein , K. , Bjerke , K. , Rognum , T. O. , Scot , H. and Valnes , K.Nature and properties of the human gastrointestinal immune system . In “ Immunology of the Gastrointestinal Tract ,” ed. Miller K. and Nicklin S. , pp. 1 – 87 ( 1987. ). CRC Press, Inc. , Boca Raton . [Google Scholar]
- 22. ) Steffen , E. K. and Berg , R. D.Relationship between caecal population levels of indigenous bacteria and translocation to the mesenteric lymph nodes . Infect. Immunol. , 39 , 1252 – 1257 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. ) Fuller , R.Probiotics in human medicine . Gut , 32 , 439 – 442 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. ) Claassen , E. , Van Winsen , R. , Posno , M. and Bocrsma , W. J. A.New and safe oral live vaccines based on Lactobacillus . In “ Advances in Mucosal Immunology ,” ed. Mestecky M. , Russell W. , Jackson S. , Michalek S. M. , Tlaskova H. and Stezl J. , pp. 1553 – 1558 ( 1995. ). Plenum Press; , New York . [PubMed] [Google Scholar]
- 25. ) Lefrancois , L.Basic aspects of intraepithelial lymphocyte immunobiology . In “ Handbook of Mucosal Immunology ,” ed. Ogra P. L. , Mestecky J. , Lamm M. , Strober W. , Bie‐nenstock J. and McGhee J. , pp. 287 – 290 ( 1994. ). Academic Press; , San Diego . [Google Scholar]
- 26. ) Zlotta , A. R. , Van Vooren , J. P. , Denis , O. , Drowart , A. , Daffe , M. , Lefevre , P. , Schandene , L. , De Cock , M. , De Bruyn , J. , Vandenbussche , P. , Jurion , F. , Palfliet , K. , Simon , J. , Schulman , C. C. , Content , J. and Huygen , K.What are the immunologically active components of Bacillus Calmette‐Guerin in therapy of superficial bladder cancer ? Int. J. Cancer , 87 , 844 – 852 ( 2000. ). [DOI] [PubMed] [Google Scholar]
- 27. ) Kitagawa , T. , Hara , M. , Sano , T. and Sugimura , T.The concept of Tenju‐gann or ‘natural cancer’ . Cancer , 83 , 1061 – 1065 ( 1998. ). [DOI] [PubMed] [Google Scholar]