Lactobacillus rhamnosus confers protection against colorectal cancer in rats
Jian Huang, Dan Wang, Anye Zhang, Qinglian Zhong, Qun Huang
Abstract
Purpose: To investigate the protective effect and mechanism of action of Lactobacillus rhamnosus against colorectal cancer (CRC). Methods: A total of 40 healthy female Sprague Dawley rats weighing 100 – 140 g (mean weight = 120 ± 20 g) were used for this study. The rats were randomly assigned to four groups of 10 rats each: normal control group, L. rhamnosus group; 1, 2-dimethylhydrazine (DMH) group and treatment group. Rats in L. rhamnosus group were inoculated with L. rhamnosus (1 x 108 CFU/mL) orally for 20 weeks, while rats in DMH group received 35 mg DMH/kg /week intraperitoneally for 10 weeks for induction of CRC. Treatment group rats received 35 mg DMH/kg bwt intraperitoneally for 10 weeks for induction of CRC, and were treated with L. rhamnosus (1 x 108 CFU/mL) orally for 20 weeks. After 20 weeks, the rats were euthanized using ether anesthesia. Expressions of inflammatory, angiogenesis and proapoptotic genes were determined using Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Treatment with L. rhamnosus significantly reduced the incidence of CRC in the rats (p < 0.05). The incidence of multiple tumors in the treatment group was also significantly reduced, when compared to DMH group (p < 0.05). The protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), cyclooxygenase-2 (COX-2), bcl-2 and vascular endothelial growth factor α (VEGF-α) were significantly upregulated in DMH group, when compared with normal control group (p < 0.05). However, treatment with L. rhamnosus significantly down-regulated the expressions of these proteins (p < 0.05). DMH treatment also significantly upregulated the expressions of iNOS, TNF-α, VEGF-α, NF-kB, β-catenin and bax genes (p < 0.05). However, L. rhamnosus significantly reversed the effects of DMH on the expression levels of these genes (p < 0.05). Conclusion: These results show that L. rhamnosus prevents CRC via suppression of expressions of inflammatory and angiogenesis genes, and upregulation of apoptotic gene expression.