Colitis-associated cancer (CAC) accounts for 2%-3% of colorectal cancer (CRC) cases preceded by inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. Intestinal microbiota has been reported to play a central role in the pathogenesis of IBD and CAC. Recently, numerous prebiotics and probiotics have being investigated as antitumor agents due to their capacity to modulate inflammatory responses. Previous studies have indicated that lactic acid bacteria could be successfully used in managing sporadic CRC, however little is known about their role in CAC.

To investigate the effect of the probiotic Lactobacillus bulgaricus (L. bulgaricus) during the development of an experimental model of colitis associated colon cancer (CAC).

C57BL/6 mice received an intraperitoneal injection of azoxymethane (10 mg/kg), followed by three cycles of sodium dextran sulphate diluted in water (5% w/v). Probiotic group received daily L. bulgaricus. Intestinal inflammation was determined by scoring clinical signs. Cytokines levels were determined from colon and/or tumor samples by ELISA BD OptEIATM kits. The level of significance was set at P < 0.05. Graphs were generated and statistical analysis performed using the software GraphPad Prism 6.0.

L. bulgaricus treatment inhibited of total tumor volume and mean size of tumors. In addition, the probiotic also attenuated the clinical signs of intestinal inflammation inducing a decrease in intestinal and tumor levels of IL-6, TNF-α, IL-17, IL-23 and IL-1β.

Our results suggest a potential chemopreventive effect of probiotic on CAC. L. bulgaricus regulates the inflammatory response and preventing CAC.

In inflammatory bowel disease, chronic inflammation results in the development of colon cancer known as colitis-associated cancer. This disease is associated with tumor necrosis factor-α (TNF-α) signaling. In addition, intestinal fibrosis is a common clinical complication that is promoted by transforming growth factor β1 (TGF-β₁). In our previous study, MA-35 attenuated renal fibrosis by inhibiting both TNF-α and TGF-β₁ signaling. This study aimed to identify the possible antitumor effects and antifibrotic effects of MA-35 using an AOM/DSS mouse model. MA-35 was orally administered every day for 70 days in the AOM/DSS mouse model. There was no difference in weight loss between the AOM/DSS group and the AOMDSS + MA-35 group, but the disease activity index score and the survival rate were improved by MA-35. MA-35 blocked the anemia and shortening of the colon induced by AOM/DSS. MA-35 reduced the macroscopic formation of tumors in the colon. In the microscopic evaluation, MA-35 reduced inflammation and fibrosis in areas with dysplasia. Furthermore, the TNF-α mRNA level in the colon tended to be reduced, and the interleukin 6, TGF-β₁ and fibronectin 1 mRNA levels in the colon were significantly reduced by MA-35. These results suggested that MA-35 inhibited AOM/DSS-induced carcinogenesis by reducing inflammation and fibrosis.

Cytokines are a family of soluble factors (Growth Factors (GFs), chemokines, angiogenic factors, and interferons), which regulate a wide range of mechanisms in both physiological and pathological conditions, such as tumor cell growth and progression, angiogenesis, and metastasis. In recent years, the growing interest in developing new cancer targeted therapies has been accompanied by the effort to characterize Tumor Microenvironment (TME) and Tumor-Stroma Interactions (TSI). The connection between tumor and stroma is now well established and, in the last decade, evidence from genetic, pharmacological, and epidemiological data supported the importance of microenvironment in tumor progression. However, several of the mechanisms behind TSI and their implication in tumor progression remain still unclear and it is crucial to establish their potential in determining pharmacological response. Many studies have demonstrated that cytokines network can profoundly affect TME, thus displaying potential therapeutic efficacy in both preclinical and clinical models. The goal of this review is to give an overview of the most relevant cytokines involved in colorectal and pancreatic cancer progression and their implication in drug response.