Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors

Abstract

The present gold standard for bladder cancer is Mycobacterium bovis, Bacillus Calmette Guerin (BCG) immunotherapy. But it has a non-responder rate of 30-50% and side effects are common. Lactobacillus casei strain Shirota has been reported to reduce the incidence of recurrence in bladder cancer patients and to cure tumor-bearing mice. Our aim was to determine if Lactobacillus rhamnosus GG (LGG) could be as efficacious as BCG in a murine model of bladder cancer. MB49 bladder cancer cells secreting human prostate-specific antigen were implanted orthotopically in female C57BL ⁄ 6 mice and urinary prostate-specific antigen levels were used as a marker of tumor growth. Mice were treated with either live or lyophilized LGG given via intravesical instillation, or both oral and intravesical LGG given once a week for a period of 6 weeks starting at day 4 after tumor implantation. A comparison of LGG and BCG immunotherapy was also carried out. LGG therapy (live or lyophilized) significantly (P = 0.006) increased the number of cured mice. Cytokine arrays and immune cell recruitment analysis revealed differences between untreated, treated, cured, and tumor-bearing mice.LGG therapy restored XCL1 levels to those in healthy bladders.LGG also recruited large numbers of neutrophils and macrophages to the tumor site. Intravesical LGG and BCG immunotherapy had cure rates of 89 and 77%, respectively, compared with 20% in untreated mice.LGG has the potential to replace BCG immunotherapy for the treatment of bladder cancer. (Cancer Sci 2010; 101: 751-758)

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

“…Therefore, more effective probiotic strains should be selected to test for the possibility of anti-tumour immunity activation and CRC prevention. In this study, two isolated strains of L. plantarum and L. rhamnosus were used as versatile lactic acid bacteria in traditional fermented products (Yu et al 2011;Qureshi et al 2014) and some species of these strains potentially regressed CRC (Geier et al 2006;Seow et al 2010;Li et al 2012).…”

“…The genera Lactobacillus are prominent probiotics members, and their beneficial effects are always outlined in various ailments such as food allergies (Kalliomäki and Isolauri 2003;Schiavi et al 2011), inflammatory bowel disease (IBD) and ulcerative colitis (UC) (Bibiloni et al 2005). Lactobacillus exerts beneficial health effects on the host by modulating humoral, cellular, or non-specific immunity, which may require interactions among microflora, epithelial cells, and immune cells (Smyth et al 2001;Christensen et al 2002;Seow et al 2010). It has also been reported that Lactobacillus can induce DC maturation and differentiation of Th1 immune response, which is important for tumour inhibition (Sun et al 2005;Ewaschuk et al 2006).…”

Lactobacillus Decelerates Cervical Epithelial Cell Cycle Progression

“…The oral intake of L. plantarum reduced colon tumors in rats [9], and L. rhamnosus implantations in mice induced bladder tumor regression [10]. However, the molecular mechanism underlying these effects remains relatively unexplored.…”

Tumor and Microenvironment Modification during Progression of Murine Orthotopic Bladder Cancer

“…In human urothelial cancer tissue, increased tumor infiltrating CD8 T cells correlates with better disease-free survival [29]. However, we have previously found that immune cells recruited to the bladder are usually located at the periphery of the tumor mass [30] and may thus be ineffective in the tumor environment. This could be caused by the immunosuppressive genes identified in this study such as CTLA4.…”