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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
Effective date (Start): June 01, 2013
Effective date (End): 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.

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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, . (13/02347-8)

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