title: Lipoteichoic acid of Bifidobacterium in combination with 5-fluorouracil inhibit tumor growth and relieve the immunosuppression.
abstract: To investigate the therapeutic efficacy of lipoteichoic acid of Bifidobacterium (BLTA) in combination with 5-fluorouracil (5-FU) treatment on the mice bearing inoculated hepatoma-22 (H(22)) cells and the effects of BLTA on immunological regulation of organism, and explore its mechanisms.
  
  
  METHODS
  Tumor-bearing mice were treated with 5-FU alone, BLTA alone or BLTA in combination with 5-FU. The tumor size were observed and measured regularly. The growth inhibiting rate (IR) of tumor was detected. MTT assay was used to evaluate the proliferation of T lymphocytes and splenic NK cell and CTL activity. Enzyme linked immunosorbent assay (ELISA) was used to detect the change of IFN-γ. FCM was used to detect T subgroup ratio of spleen cells of tumor-bearing mice. Expression change of mRNA and proteins of Foxp3 and TIM-3 were detected by Real-Time-PCR and Western blot in tumor-bearing mice tumor tissue.
  
  
  RESULTS
  Both 5-FU and BLTA had inhibition effect on tumor-growth. While in the 5-FU + BLTA group, the inhibition of tumor growth was more significant, with increased T lymphocyte proliferation and IFN-γproduction of spleen cells. Spleen cells of tumor-bearing mice had high CD4(+)CD25(+)regulatory T cell (CD4(+)CD25(+)T(reg)) ratio and high mRNA and proteins expression of Foxp3 and TIM-3, but in the BLTA and 5-FU group, CD4(+)CD25(+)T(reg) ratio degraded, with down regulation mRNA and proteins expression of Foxp3 and TIM-3. But CD4(+) T cells also decreased in spleen cells of tumor-bearing mice by alone 5-FU treated, splenic NK cell and CTL activity also degraded, while CD4(+) T cells and splenic NK cell and CTL activity significantly increased by BLTA treated. BLTA in combination with 5-FU could also enhance the ratio of CD4(+) T cells and splenic NK cell and CTL activity.
  
  
  CONCLUSIONS
  The present study suggested that BLTA in combination with 5-FU could enhance antitumor effect, with inhibiting TIM-3/TIM-3L pathway, cutting down immunosuppressive activity of CD4(+)CD25(+) T(reg) and enhancing cell-mediated immunity.
authors.affiliation: The Affiliated Hospital of North Sichuan medical college, Department of Clinical Laboratory, 63 # WenHua Road, Nanchong, Sichuan, 637000, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Fu-rong
authors.initials: FR
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001644:Bifidobacterium / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013682:Teichoic Acids / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011991:Receptors, Virus; D013682:Teichoic Acids; C009900:lipoteichoic acid; D007371:Interferon-gamma; D005472:Fluorouracil