Skip to main content
SpringerLink
Log in

Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice

Journal of Biosciences Aims and scope Submit manuscript

Cite this article

Abstract

Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN-γ (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Abbreviations

APC:

allophycocyanin

CFU:

colony forming unit

CRC:

colorectal cancer

DC:

dendritic cells

ELISA:

enzyme-linked immunosorbent assay

FITC:

fluorescein isothiocyanate

IFN:

interferon

IL:

interleukin

MRS:

deMan, Rogosa and Sharpe

NK:

natural killer cells

PE:

phycoerythrin

References

  • Abou-Elkacem L, Arns S, Brix G, Gremse F, Zopf D, Kiessling F and Lederle W 2013 Regorafenib inhibits growth, angiogenesis, metastasis in a highly aggressive, orhotopic colon cancer model. Mol. Cancer Ther. 12 1322–1331

    Article  CAS  PubMed  Google Scholar 

  • Al-Hassi HO, Mann ER, Sanchez B, English NR, Peake ST, Landy J, Man R, Urdaci M, et al. 2014 Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Mol. Nutr. Food Res. 58 1132–1143

    Article  CAS  PubMed  Google Scholar 

  • Arthur JC, Gharaibeh RZ, Uronis JM, Perez-Chanona E, Sha W, Tomkovich S, Mühlbauer M, Fodor AA, et al. 2013 VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci. Rep. 3 1–9

    Article  Google Scholar 

  • Azcárate-Peril MA, Sikes M and Bruno-Bárcena JM 2011 The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am. J. Physiol. Gastrointest. Liver. Physiol. 301 G401–G424

    Article  PubMed Central  PubMed  Google Scholar 

  • Bäuerl C, Llopis M, Antolín M, Monedero V, Mata M, Zúñiga M, Guarner F and Martínez GP 2013 Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa. Genes Nutr. 8 165–180

    Article  PubMed Central  PubMed  Google Scholar 

  • Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, De Simone C and Sartor RB 2005 VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am. J. Gastroenterol. 100 1539–1546

    Article  PubMed  Google Scholar 

  • Chen L, He Z, Qin L, Li Q, Shi X, Zhao S, Chen L, Zhong N, et al. 2011 Antitumor effect of Malaria Parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity. PLoS One 6 1–10

    Google Scholar 

  • Chien CC, Lin WC, Kong MS, Shi HN, Allan Walker W, Lin CY, Huang CT, Lin YC, et al. 2012 Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue. Br. J. Nutr. 107 1623–1634

    Article  Google Scholar 

  • Christensen HR, Frøkiær H and Pestka JJ 2002 Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J. Immunol. 168 171–178

    Article  CAS  PubMed  Google Scholar 

  • Delcenserie V, Martel D, Lamoureux M, Amiot J, Boutin Y and Roy D 2008 Immunomodulatory effects of probiotics in the intestinal tract. Curr. Issues Mol. Biol. 10 37–54

    CAS  PubMed  Google Scholar 

  • Dwivedi A, Nomikou N, Nigam PS and McHale AP 2012 The effects of microencapsulated Lactobacillus casei on tumour cell growth: in vitro and in vivo studies. Int. J. Med. Microbiol. 302 293–299

    Article  CAS  PubMed  Google Scholar 

  • Erickson KL and Hubbrad NE 2000 Probiotic immunomodulation in health and disease. J. Nutr. 130 403–409

    Google Scholar 

  • Evans C, Dalgleish AG and Kumar D 2006 Review article: immune suppression and colorectal cancer. Aliment. Pharmacol. Ther. 24 1163–1177

    Article  CAS  PubMed  Google Scholar 

  • Ewaschuk JB, Walker JW, Diaz H and Madsen KL 2006 Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice. J. Nutr. 136 1483–1487

    CAS  PubMed  Google Scholar 

  • Francois P, Douillard AR, Kant R, Taija E, Pietilä HM, Järvinen MM, Cinzia L, Randazzo LP, et al. 2013 Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG. PLoS Genet. 9 1–15

    Google Scholar 

  • Gao X and Xiong S 2011 Medical immunology 2nd ed., Vol. 80 (Beijing: Higher Education Press) p 144

    Google Scholar 

  • Geier MS, Butler RN and Howarth GS 2006 Probiotics, Prebiotics and Synbiotics: A Role in Chemoprevention for Colorectal Cancer? Cancer Biol. Therapy 5 1265–1269

    Article  CAS  Google Scholar 

  • Ghoneum M and Gollapudi S 2004 Induction of apotosis in breast cancer cells by Saccharomyces Cerevisiae, the baker’s yeast, in vitro. Anticancer Res. 24 1455–1464

    PubMed  Google Scholar 

  • Hirayama K and Rafter J 2000 The role of probiotic bacteria in cancer prevention. Microbes Infect. 2 681–686

    Article  CAS  PubMed  Google Scholar 

  • Horinaka M, Yoshida T, Kishi A, Akatani K, Yasuda T, Kouhara J, Wakada M and Sakai T 2010 Lactobacillus strains induce TRAIL production and facilitate natural killer activity against cancer cells. FEBS Lett. 584 577–582

    Article  CAS  PubMed  Google Scholar 

  • Hu J, Zhu S, Xia X, Zhang L, Kleinerman ES and Li S 2014 CD8+ T cell-specific induction of NKG2D receptor by doxorubicin plus interleukin-12 and its contribution to CD8+ T cell accumulation in tumors. Mol. Cancer 13 34

    Article  PubMed Central  PubMed  Google Scholar 

  • Jemal A, Siegel R, Xu J and Ward E 2010 Cancer statistics. CA Cancer J. Clin. 60 277–300

    Article  PubMed  Google Scholar 

  • Kalliomäki M and Isolauri E 2003 Role of intestinal flora in the development of allergy. Curr. Opin. Allergy Clin. Immunol. 3 15

    Article  PubMed  Google Scholar 

  • Kandasamy M, Bay B-H, Lee Y-K and Mahendran R 2011 Lactobacilli secreting a tumor antigen and IL-15 activates neutrophils and dendritic cells and generates cytotoxic T lymphocytes against cancer cells. Cell. Immunol. 271 89–96

    Article  CAS  PubMed  Google Scholar 

  • Lee JW, Shin JG, Kim EH, Kang HE, Yim IB, Kim JY, Joo HG and Woo HJ 2004 Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacrerium longum. J. Vet. Sci. 5 41–48

    PubMed  Google Scholar 

  • Li S, Zhao Y, Zhang L, Zhang X, Huang L, Li D, Niu C, Yang Z, et al. 2012 Antioxidant activity of Lactobacillus plantarum strains isolated from traditional Chinese fermented foods. Food Chem. 135 1914–1919

    Article  CAS  PubMed  Google Scholar 

  • Linsalata M and Russo F 2008 Nutritional factors and polyamine metabolism in colorectal cancer. Nutrition 24 382–389

    Article  CAS  PubMed  Google Scholar 

  • Liong MT 2008 Roles of probiotics and prebiotics in colon cancer prevention: Postulated mechanisms and in vivo evidence. Int. J. Mol. Sci. 9 854–863

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maassen CB, van Holten-Neelen C, Balk F, den Bak-Glashouwer MJ, Leer RJ, Laman JD, Boersma WJ and Claassen E 2000 Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains. Vaccine 18 2613–2623

    Article  CAS  PubMed  Google Scholar 

  • Maroof H, Hassan ZM, Mobarez AM and Mohamadabadi MA 2012 Lactobacillus acidophilus could modulate the immune response against breast cancer in murine model. J. Clin. Immunol. 32 1353–1359

    Article  CAS  PubMed  Google Scholar 

  • Marshall JR 2008 Prevention of colorectal cancer: diet, chemoprevention, and lifestyle. Gastroenterol. Clin. N. Am. 37 73–82

    Article  Google Scholar 

  • Mohamadzadeh M, Olson S, Kalina WV, Ruthel G, Demmin GL, Warfield KL, Bavari S and Klaenhammer TR 2005 Lactobacilli activate human dendritic cells that skew T cells toward T-helper 1 polarization. Proc. Natl. Acad. Sci. USA 7 1155–1164

    Google Scholar 

  • Mohamadzadeh M, Duong T, Hoover T and Klaenhammer TR 2008 Targeting mucosal dendritic cells with microbial antigens from probiotic lactic acid bacteria. Expert Rev. Vaccines 7 163–174

    Article  CAS  PubMed  Google Scholar 

  • Narushima S, Sakata T, Hioki K, Itoh T, Nomura T and Itoh K 2010 Inhibitory effect of yogurt on aberrant crypt foci formation in the rat colon and colorectal tumorigenesis in RasH2 mice. Exp. Anim. 59 487–494

    Article  CAS  PubMed  Google Scholar 

  • Ni J, Galani IE, Cerwenka A, Schirrmacher V and Fournier P 2011 Antitumor vaccination by Newcastle Disease Virus Hemagglutinin–Neuraminidase plasmid DNA application: changes in tumor microenvironment and activation of innate anti-tumor immunity. Vaccine 29 1185–1193

    Article  CAS  PubMed  Google Scholar 

  • Osterlund P, Ruotsalainen T, Korpela R, Saxelin M, Ollus A, Valta P, Kouri M, Elomaa I, et al. 2007 Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomized study. Br. J. Cancer 97 1028–1034

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qiao J, Kottke T, Willmon C, Galivo F, Wongthida P, Diaz RM, Thompson J, Ryno P, et al. 2008 Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy. Oncolytic Virotherapy Immunother. 14 37–44

    CAS  Google Scholar 

  • Qureshi A, Itankar Y, Ojha R, Mandal M, Khardenavis A and Kapley A 2014 Genome sequence of Lactobacillus plantarum EGD-AQ4, isolated from fermented product of Northeast India. Genome Announcements 2 1–2

    Article  Google Scholar 

  • Rafer J 2003 Probiotics and colon cancer. Best Pract. Res. Clin. Gastroenterol. 17 849–859

    Article  Google Scholar 

  • Schiavi E, Barletta B, Barone A, Butteroni C, Corinti S and DiFelice G 2011 Probiotic treatment induces intestinal regulatory dendritic and T cells, and counter-regulates Th2 responses and anaphylaxis in a mouse model of food allergy. Clin. Transl. Allergy 1 1

    Article  Google Scholar 

  • Seow SW, Cai S, Rahmat JN, Bay BH, Lee YK, Chan YH and Mahendran R 2010 Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors. Cancer Sci. 101 751–758

    Article  CAS  PubMed  Google Scholar 

  • Shen H, Tang G, Zeng G, Yang Y, Cai X, Li D, Liu H and Zhou N 2013 Purification and characterization of an anti-tumor polysaccharide from Portulaca oleracea L. Carbohydr. Polym. 93 395–400

    Article  CAS  PubMed  Google Scholar 

  • Smyth MJ, Cretney E, Takeda K, Wiltrout RH, Sedger LM, Kayagaki N, Yagita H and Okumura K 2001 Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon c-dependent natural killer cell protection from tumor metastasis. J. Exp. Med. 3 661–670

    Article  Google Scholar 

  • Sun J, Shi YH, Le GW and Ma XY 2005 Distinct immune response induced by peptidoglycan derived from Lactobacillus sp. World J. Gastroenterol. 11 6330–6337

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takagi A, Matsuzaki T, Sato M, Nomoto K, Morotomi M and Yokokura T 2001 Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism. Carcinogenesis 22 599–605

    Article  CAS  PubMed  Google Scholar 

  • Wang SM, Zhang LW, Fan RB, Han X, Yi HX, Zhang LL, Xue CH, Li HB, et al. 2014 Induction of HT-29 cells apoptosis by lactobacilli isolated form fermented products. Institut Pasteur. 165 202–214

  • Wykes MN, Liu XQ, Jiang S, Hirunpetcharat C and Good MF 2007 Systemic tumor necrosis factor generated during lethal Plasmodium infections impairs dendritic cell function. J. Immunol. 179 3982–3987

    Article  CAS  PubMed  Google Scholar 

  • Yazdi MH, Mahdavi M, Setayesh N, Esfandyar M and Shahverdi AR 2013 Selenium nanoparticle-enriched Lactobacillus brevis causes more efficient immune responses in vivo and reduces the liver metastasis in metastatic from of mouse breast cancer. DARU J. Pharm. Sci. 21 33–41

    Article  CAS  Google Scholar 

  • Yu J, Wang WH, Menghe BLG, Jiri MT, Wang HM, Liu WJ, Bao QH, Lu Q, et al. 2011 Diversity of lactic acid bacteria associated with traditional fermented dairy products in Mongolia. J. Dairy Sci. 94 3229–3241

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31302061), the Ministry of Education University Doctoral Fund (20110061110005), and Chinese Special Fund for Agro-Scientific Research in the Public Interest (201303033).

Author information

Authors and Affiliations

  1. College of Veterinary Medicine, Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, 130062, China

    Jingtao Hu & Zhuang Ding

  2. College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China

    Jingtao Hu, Chunfeng Wang, Liping Ye, Wentao Yang, Haibin Huang, Fei Meng & Shaohua Shi

  3. Guangxi Veterinary Research Institute, 51 You Ai Road, Nanning, Guangxi, 530001, China

    Fei Meng

Authors
  1. Jingtao Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunfeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liping Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wentao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haibin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fei Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shaohua Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhuang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chunfeng Wang or Zhuang Ding.

Additional information

Corresponding editor: Murali Bashyam

[Hu J, Wang C, Ye L, Yang W, Huang H, Meng F, Shi S and Ding Z 2015 Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice. J. Biosci. 40 1–11] DOI 10.1007/s12038-015-9518-4

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, J., Wang, C., Ye, L. et al. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice. J Biosci 40, 269–279 (2015). https://doi.org/10.1007/s12038-015-9518-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-015-9518-4

Keywords

search

Navigation