The effect of 15d-PGJ2 on multiple myeloma cell line development in vitro and in vivo

• Grant number: 13/02347-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2013
• End date: May 31, 2015
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Marcelo Henrique Napimoga
• Grantee: Marcelo Sperandio
• Host Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil

Abstract

Multiple mieloma (MM) is a systemic malignant neoplasm, which represents 2% of all cancer-related deaths. Despite advances in therapy, treatment resistance and eventual relapse are still a cause for concern. Neoplasm development is always associated with COX signaling imbalance, where COX-2 overexpression is associated with poor prognosis. 15-d-PGJ2 is a COX-2 selective inhibitor that has been shown to induce apoptosis in tumour cells both as a direct PPAR³ ligand, as well as by inactivating the phosphorilation of IKK and Ikappa², thus bypassing drug resistance. The aim of this study will be to investigate both in vitro and in vivo the chemotherapic value of 15d-PGJ2 in MM tumours. In vivo experiments will involve MM cell lines treated with 15d-PGJ2 in terms of the oxidative stress enzymes peroxiredoxine (Prx) I and IV expression. The in vivo arm of the study will involve xenotransplantation of MM cell lines into SCID mice that will subsequently be treated with 15d-PGJ2 or placebo. The tumours will eventually be histopathologically analysed and Prx expression investigated via immunohistochemistry and Western blotting.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SPERANDIO, MARCELO; DEMASI, ANA PAULA D.; MARTINEZ, ELIZABETH F.; SAAD, SARA O.; PERICOLE, FERNANDO V.; VIEIRA, KARLA P.; FREITAS, NADIR S.; ARAUJO, VERA C.; BROWN, AMY LOUISE; CLEMENTE-NAPIMOGA, JULIANA TRINDADE; et al. 15d-PGJ(2) as an endoplasmic reticulum stress manipulator in multiple myeloma in vitro and in vivo. Experimental and Molecular Pathology, v. 102, n. 3, p. 434-445, JUN 2017. (13/02347-8)