Lactobacillus Attenuate the Progression of Pancreatic Cancer Promoted by Porphyromonas Gingivalis in K-rasG12D Transgenic Mice

Abstract

Accumulating evidence suggests that there is a link between the host microbiome and pancreatic carcinogenesis, and that <i>Porphyromonas gingivalis (P. gingivalis)</i> increases the risk of developing pancreatic cancer. The aim of the current study was to clarify the role of <i>P. gingivalis</i> in the pathogenesis of pancreatic cancer and the potential immune modulatory effects of probiotics. The six-week-old LSL-K-rasG12D; Pdx-1-cre (KC) mice smeared P. gingivalis on the gums, causing pancreatic intraepithelial neoplasia (PanIN) after four weeks to be similar to the extent of lesions in untreated KC mice at 24 weeks. The oral inoculation of <i>P. gingivalis</i> of six-week-old <i>LSL-K-ras^G12D</i>; <i>Pdx-1-cre</i> (KC) mice caused significantly pancreatic intraepithelial neoplasia (PanIN) after treatment four weeks is similar to the extent of lesions in untreated KC mice at 24 weeks. The pancreas weights of <i>P. gingivalis</i> plus probiotic-treated mice were significantly lower than the mice treated with <i>P. gingivalis</i> alone (<i>P</i> = 0.0028). The histological expressions of Snail-1, ZEB-1, collagen fibers, Galectin-3, and PD-L1 staining in the pancreas were also notably lower. In addition, probiotic administration reduced the histological expression of Smad3 and phosphorylated Smad3 in <i>P. gingivalis</i> treated KC mice. We demonstrated that oral exposure to <i>P. gingivalis</i> can accelerate the development of PanIN lesions. Probiotics are likely to have a beneficial effect by reducing cancer cell proliferation and viability, inhibiting PanIN progression, and cancer cell metastasis (Epithelial-mesenchymal transition, EMT). The transforming growth factor-β signaling pathway may be involved in the tumor suppressive effects of probiotics.