Combination Therapy Using Heat-Killed Lactobacillus Casei and Bacillus Coagulans Along with Alpha-Galactosyl Ceramide in a Mouse Model of Colorectal Cancer.

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Current treatments for CRC, in addition to side effects, face limitations such as drug resistance and selective ineffectiveness, which can reduce treatment efficacy. Researchers are seeking new cancer treatment methods to improve patients' quality of life by reducing side effects and increasing effectiveness. Objective: The aim of this research was to evaluate the efficacy of a novel therapeutic method that combines heat-killed Lactobacillus casei (L.C) and Bacillus coagulans (B.C) with alpha-galactosyl ceramide in a mouse model of CRC. Materials and Methods: CT26 cells were injected subcutaneously into the right flanks of female BALB/c mice aged 6 to 8 weeks (n=60). After the tumors became palpable, the mice were divided into six equal groups to begin therapy. The control group received phosphate-buffered saline (PBS), while the experimental groups were treated with heat-killed L.C and B.C, α-GalCer, a combination of these treatments, and 5-FU. The treatments were administered to the tumor-bearing mice twice, with a one-week interval between each dose. The survival probability and tumor size were recorded during the study. Then, the mice were euthanized, and sampling was performed for laboratory investigations. Results: Evaluations showed that all treatment groups led to increased survival probability and reduced tumor size compared to the control group (P<0.05). Also, cytokines assays revealed that all trearments caused increased IFN-γ secretion (P<0.05), and decreased IL-4 (P<0.05) and TGF-β (P<0.05) (except for B.C, α-GalCer and 5-FU groups P>0.05). Additionally, all treatment enhanced nitric oxide (NO) and lactate dehydrogenase (LDH) production of spelonocytes compared to the control group (P<0.05). All the mentioned changes related to the evaluation indicators in the combined treatment group were greater than in the other treatment groups (P<0.05) (except for tumor size). Conclusion: It appears that the combination of natural products in treatment of CRC may serve as an effective complementary therapy alongside chemotherapy, yielding positive outcomes in the mouse model of CRC.