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Resistance of oral cancer cells to 5‐ALA‐mediated photodynamic therapy
Author(s) -
Rosin Flávia Cristina P.,
Teixeira Marina Gabriela,
Pelissari Cibele,
Corrêa Luciana
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26541
Subject(s) - photodynamic therapy , survivin , pi3k/akt/mtor pathway , cancer research , protein kinase b , protoporphyrin ix , apoptosis , viability assay , cancer , cell growth , cancer cell , cell , cyclin d1 , chemistry , biology , medicine , cell cycle , biochemistry , organic chemistry
Abstract Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio‐resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti‐apoptotic proteins and those related to Akt/mTOR pathway. Sub‐lethal doses of PDT were applied, consisting of a constant concentration of 5‐aminolevulinic acid (5‐ALA) (1 mM, 4‐h incubation) and increasing irradiation dose with LED (from 5.86 to 10.54 J/cm 2 ). Cell viability, migration capacity, intracellular expression of protoporphyrin IX (PpIX), mitochondrial density, and pro‐survival proteins were investigated in PDT‐resistant cells. Six OSCC cell generations resistant to PDT were isolated. The resistant cells exhibited a survival phenotype characterized by a reduction in the expression of endogenous PpIX, increase in mitochondrial density, increase in migration capacity, and up‐regulation of p‐NFκB, p‐survivin, iNOS, p‐Akt Ser 473 , cyclin D1, p‐mTOR Ser 2481 , and p‐mTOR Ser 2448 . OSCC cells are able to survive doses of 5‐ALA‐PDT by reducing PpIX synthesis and activating signaling pathways related to the inhibition of apoptosis and improvement of cell proliferation. Further studies are necessary to confirm whether this PDT‐resistance phenotype can be clinically present, mainly in OSCC showing clinical recurrences after exposure to different PDT protocols.