Lactobacillus rhamnosus Enhances the Immunological Antitumor Effect of 5-Fluorouracil against Colon Cancer

Pak J Biol Sci. 2019 Jan;22(12):597-606. doi: 10.3923/pjbs.2019.597.606.

Abstract

Background and objectives: 5-Fluorouracil (5-FU) is the most common anticancer therapeutic, even though its response rate as a single agent is usually less than 20%. Lactobacillus rhamnosus bacteria reduce the severity of gastrointestinal tract infections, with additional functions in cancer prevention. This study investigated the histological and immunological changes associated with the combination treatment of L. rhamnosus and 5-FU in mice with colon cancer.

Material and methods: Five groups of male mice were classified as follows; Group A: Mice injected with azoxymethane (AOM) to induce colon cancer, Group AL: Mice injected with AOM and orally administered L. rhamnosus alone, Group AF: Mice injected with AOM and administered 5-FU, Group AFL: Mice injected with AOM and treated with both L. rhamnosus and 5-FU and Group C: Untreated control mice.

Results: A reduction in inflammatory features with a normal histological structure was observed in the colon of the AFL group compared to those in the other treated groups. The intestinal mucosa of the AFL group showed a significant downregulation in K-ras and Treg/IL-10 transcription levels. This downregulation was associated with an improvement in the innate and adaptive immune responses through increased TLR2 and Th1/IFNγ transcription. TNFα and IL-6 protein expression was significantly elevated in the serum of the AFL groups compared to levels in both the A and AF groups.

Conclusion: This study provides evidence about the potential immunological influence of L. rhamnosus when used in combination with 5-FU as a novel colon cancer therapeutic strategy.

Keywords: 5-fluorouracil; Colon cancer; L. rhamnosus; antitumor immune response; cytokines; probiotics.

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Combined Modality Therapy
  • Fluorouracil / administration & dosage*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Immunity, Innate
  • Interleukin-6 / blood
  • Lacticaseibacillus rhamnosus*
  • Male
  • Mice
  • Probiotics / administration & dosage*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antineoplastic Agents
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)
  • Fluorouracil