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Resistance of oral cancer cells to 5-aminolevulinic acid mediated-photodynamic therapy

Grant number: 14/10380-8
Support type:Regular Research Grants
Duration: December 01, 2014 - November 30, 2016
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Luciana Corrêa
Grantee:Luciana Corrêa
Home Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is a high morbidity cancer, which leads high frequency of recurrence and resistance to conventional treatments. Photodynamic therapy (PDT) has been applied in early phases of OSCC, with a number of cases showing promising indexes of complete remission of the tumor. It is unknown, however, if OSCC cells can be resistant to the PDT, mainly in situations of repetitive cycles of this therapy using sublethal doses. The aim of this study is to verify if human and animal OSCC cells develop resistance to 5 aminolevulinic acid (5-ALA)-mediated PDT, as well as if mechanisms of antiapoptosis, of cell cycle inhibition, and of autophagy control are involved in this process. SCC9 cells will be submitted to repetitive cycles with crescent doses of 5-ALA-mediated PDT, until they exhibit increase on viability in relation to that observed with initial doses. Indexes of apoptosis and levels of proteins linked to mechanisms of antiapoptosis (iNOS, NFkB, Mcl-1, bcl-2, and survivin), to cell cycle modulation (IKK, Akt, and cyclin D1), and to autophagy inhibition (mTOR) will be determined. Celecoxibe will be administered in the resistant cell clones, in order to investigate if this anti-inflammatory drug promotes inhibition of these proteins and, consequently, increases the PDT efficacy. In vivo experiment with OSCC induction in rats using 4-NQO carcinogenesis model will be also conducted. Induced malignant lesions will be treated with 5-ALA-mediated PDT. Immunohistochemical tests will be performed in the treated lesions, analyzing the expression of the cited proteins in resistant malignant cells. It is expected elucidate if it is possible to induce OSCC cells resistant to the PDT, as well as if the celecoxib exerts synergic effect on this therapy, increasing its efficacy on these situations. (AU)

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)
ROSIN, FLAVIA CRISTINA P.; TEIXEIRA, MARINA GABRIELA; PELISSARI, CIBELE; CORREA, LUCIANA. Resistance of oral cancer cells to 5-ALA-mediated photodynamic therapy. Journal of Cellular Biochemistry, v. 119, n. 4, p. 3554-3562, APR 2018. Web of Science Citations: 4.

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