In vitro and in vivo effects of treatment with leucine, progesterone, sitagliptin and liraglutide on inflammatory and cell proliferation pathways mechanisms in placentas exposed to cyclophosphamide and doxorubicin chemotherapy

• Grant number: 21/08188-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Carla de Moraes Salgado
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia, AP.TEM
• Associated scholarship(s): 24/07813-1 - IMPACT OF CHEMOTHERAPEUTIC DRUGS ON TROPHOBLAST ORGANOID FUNCTION AND SECRETORY PROFILE, BE.EP.DR

Abstract

Chemotherapy during pregnancy can be safely recommended, beging in the second trimester of pregnancy. However, placental exposure to chemotherapy is associated with its developmental failures that lead to fetal growth restriction, due to inflammatory pathways activit and synthesis pathways downregulated on placental tissue. Some treatments, such as leucine, progesterone, sitagliptin and liraglutide, could be a modulatory actions on inflammatory and cell proliferation pathways. Thus, this study has as objective to evaluate, in vitro and in vivo, the leucine, sitagliptin, liraglutide and progesterone effects on inflammatory and cell synthesis pathways in placentas exposed to chemotherapy cyclophosphamide and doxorubicin. In vitro model, BeWo cells will be distributed at groups: CT (Control): no treatment; CD: with cyclophosphamide and doxorubicin; C: cyclophosphamide administration; D: doxorubicin administration. The four experimental groups will be subjected to treatments with leucine, sitagliptin and liraglutide. RNAseq will be performed to investigate possible candidate genes to be correlated with changes in inflammatory pathways and cell synthesis and proliferation. In vivo model, pregnant Wistar rats will be distributed into the following groups: C (Control): no treatment; W: with tumor implant; WCD: with tumor implant and cyclophosphamide and doxorubicin administration; WCD + treatment: with tumor implant, cyclophosphamide and doxorubicin administration plus treatment. In WCD + treatment group, the treatment to be carried out will depend on the in vitro results, which may be with leucine, sitagliptin and liraglutide. PCR analysis of genes will be performed and evaluated by RNAseq, as well as Western Blot of related proteins.