Helminth-derived Molecules improve 5-Fluorouracil Treatment on experimental colon tumorigenesis 

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B976
Abstract ID: 7971

Presenting Author:
Luis I Terrazas , Professor at Univ. Nacional Autónoma de México Fac. de Estudios Superiores Iztacala

Abstract:

Colorectal cancer is one of the most prevalent fatal neoplasias worldwide. The mortality rate of patients is still nearly 50%. The conventional and first-line chemotherapeutic agent utilized is 5-fluorouracil (5FU). However, it has low efficiency. Combination treatment with leucovorin and oxaliplatin or irinotecan improves the effectiveness of 5FU therapy. Unfortunately, most patients develop drug resistance in advanced stages, leading to disease progression. Here, we evaluated the role of helminth-derived Taenia crassiceps (TcES) molecules as an alternative adjuvant for 5FU in treating advanced colitis-associated colon cancer. TcES enhanced the effects of 5FU on established colonic tumors by reducing colonic tumors and the expression of Il-10 and Tgf-b, and proinflammatory cytokines, such as Tnf-a and Il-17a, and downregulating the levels of molecular markers associated with malignancy, cyclin D1, and Ki67, both involved in apoptosis inhibition and the signaling pathway of β-catenin. TcES+5FU therapy promoted NK cell recruitment and the release of Granzyme B1 at the tumor site, inducing tumor cell death. It restored P53 activity and downregulated Mdm2 expression. In vitro assays with human colon cancer cell lines showed that TcES+5FU significantly reduced cell proliferation and migration by modulating the P53 and P21 signaling pathways. Our findings demonstrate that helminth-derived excreted/secreted products may potentiate the effect of 5FU on established colon tumors.