Isolation and characterization of squamous carcinoma cells resistant to photodynamic therapy

Milla, Laura; Cogno, Ingrid Sol; Rodríguez, Matías Exequiel; Sanz-Rodrı́guez, Francisco; Zamarrón, Alicia; Gilaberte, Yolanda; Carrasco, Elisa; Rivarola, Viviana; Juarranz, Ángeles

doi:10.1002/jcb.23145

Cited by 46 publications

(69 citation statements)

References 44 publications

(47 reference statements)

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“…Com base nos modelos de resistência a PDT descritos na literatura, a primeira dose de PDT deve gerar 90% de letalidade (DL90) (Milla et al, 2011;Zamarrón et al, 2011 (Milla et al, 2011).…”

Section: Methodsunclassified

“…Os trabalhos descritos na literatura, em geral, utilizaram Fs com localização na mitocôndria, basicamente porfirinas, no desenvolvimento de resistência a PDT (Casas et al, 2011 (Milla et al, 2011). Contudo não foi possível estabelecer uma população de glioma humano resistente à PDT mediada por esse Fs (Madsen et al, 2003;Hirschberg et al, 2006).…”

Section: Mecanismos De Resistência Tumoral à Terapia Fotodinâmicaunclassified

“…Esse ensaio foi realizado com base nos resultados da literatura que demonstraram haver menor quantidade de PpIX em células resistentes à PDT (Milla et al, 2011;Casas et al, 2006 …”

Section: Quantificação Da Protoporfirina IXunclassified

“…Nos artigos sobre resistência a PDT, a população celular que exibe viabilidade 1,5 vezes maior do que a população parental (população original) pode ser considerada como resistente, diante de dose que induza 90% de letalidade (DL90) (Milla et al, 2011;Zamarrón et al, 2015;Singh et al, 2001 (Milla et al, 2011). O cariótipo poliplóide das células resistentes a PDT já foi relatado anteriormente em células de fibrossarcoma induzido por radiação (Sharkey et al, 1993).…”

Section: Gruposunclassified

“…Esse FS tem sido utilizado para casos de lesões potencialmente malignais na cavidade bucal (Chen et al, 2005;Tsai et al, 2004), bem como para carcinomas verrucosos e CEC pouco invasivos Fan et al, 1996). Há estudos demonstrando que ciclos repetidos de PDT mediada pelo 5-ALA (5-ALA-PDT) podem gerar resistência em células de CEC cutâneo (Milla et al, 2011) e de adenocarcinoma mamário murino (Casas et al, 2006). Porém não encontramos nenhum trabalho que tenha avaliado se células de CEC bucal desenvolvem resistência a essa terapia, nem tampouco as vias de sinalização que poderiam estar associadas a essa resistência.…”

Section: Introductionunclassified

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Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

Rosin¹

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A minha Orientadora, Prof a . Dr a . Luciana Corrêa, por sempre ouvir e discutir comigo todas as questões e dúvidas que surgiram durante o desenvolvimento desta tese e por ser essa pessoa tão generosa, inteligente e acessível. Admiro-a muito como pessoa e pesquisadora.Ao Prof. Dr. Moacir Novelli, que durante suas visitas ao laboratório sempre alegrava meu dia e por compartilhar comigo um pouco da sua imensa sabedoria. A Marina, a única companheira de profissão da Pós, que sempre esteve disposta a me ajudar e me ouvir, pela amizade, carinho e companheirismo. Pelos nossos cafés da manhã que sempre tornava meu dia mais leve e agradável.A Karla, pelo bom humor constante que sempre alegrava meu dia, por sempre me ouvir, me apoiar e pelos nossos cafezinhos.A Gabriela, por sempre estar ao meu lado me dando força e apoio, pelos nossos almoços diários na copa do departamento que tornavam meu dia mais alegre e por todo carinho e amizade.A Lara, pela amizade e por todo carinho e apoio. Por ser essa pessoa tão agradável e acessível por sempre estar disposta a me ourvir. Tenho a impressão de ter sido uma criança brincando à beira-mar, divertindo-me em descobrir uma pedrinha mais lisa ou uma concha mais bonita que as outras, enquanto o imenso oceano da verdade continua misterioso diante de meus olhos". Oral squamous cell carcinoma (SCC) is a malignant tumor with high morbidity and mortality rates, and it is difficult to treat. Conventional treatment for oral SCCs includes surgery and radiotherapy that may be followed by chemotherapy. Although these treatments are widely used, they are ineffective against some resistant tumors. Isaac Newton RESUMOOncologic photodynamic therapy (PDT) has been used as an adjuvant treatment for oral SCCs, especially in less invasive cases that require tumor reduction before surgical resection. However, like conventional treatments, PDT can induce the occurrence of resistant cell populations such as cutaneous carcinomas and colon and breast adenocarcinomas. The hypothesis that oral SCCs develop resistance to PDThas not yet been tested. Therefore, the aims of this study were to investigate whether oral SCCs (SCC9) develop resistance to several cycles of 5-aminolevulinic acidmediated PDT (5-ALA-PDT) and to determine whether the expression of markers associated with cell survival (NFB, Bcl-2, iNOS, mTOR, and Akt) is altered during this process. An oral SCC (SCC9) cell line was used, which was subjected to the following conditions: 1) Control: cultured without any treatment; 2) ALA: incubated with 5-ALA (1 mM for 4 h); 3) LED: treated with LED light (630 nm, 5.86 J/cm 2 , 22.5 J, 150 mW, 150 s); and 4) PDT: treated with 5-ALA-PDT (with the protocols of the ALA and LED groups combined) generating a lethal dose of 90%. Initially, only one cycle of PDT was administered, and cell viability was determined in all groups 24, 48, 72, and 120 h after irradiation. Subsequently, the DNA fragmentation detection assay (TUNEL) and immunofluorescence analysis of the expression of proteins NFB, Bcl-2, iNOS, pmTOR, ...

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Section: Methodsunclassified

Section: Mecanismos De Resistência Tumoral à Terapia Fotodinâmicaunclassified

“…Esse ensaio foi realizado com base nos resultados da literatura que demonstraram haver menor quantidade de PpIX em células resistentes à PDT (Milla et al, 2011;Casas et al, 2006 …”

Section: Quantificação Da Protoporfirina IXunclassified

Section: Gruposunclassified

Section: Introductionunclassified

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Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

Rosin¹

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Reversal of the Migratory and Invasive Phenotype of Ras-Transfected Mammary Cells by Photodynamic Therapy Treatment

et al. 2016

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Photodynamic therapy (PDT) is a non-thermal technique for inducing tumor damage following administration of a light-activated photosensitizing drug (PS). In a previous work we found that PDT induces cytoskeleton changes in HB4a-Ras cells (human mammary breast carcinoma HB4a cells transfected with the RAS oncogene). In the present work we have studied the migratory and invasive features and the expression of proteins related to these processes on HB4a-Ras cells after three successive cycles of PDT using different PSs: 5-aminolevulinic acid (ALA), Verteporfin (Verte), m-tetrahydroxyphenylchlorin (m-THPC), and Merocyanine 540 (MC). A slight (1.25- to 2-fold) degree of resistance was acquired in cell populations subjected to the three successive PDT treatments. However, complete cell killing was achieved after a light dose increase. Regardless of the PS employed, all the PDT-treated populations had shorter stress fibres than the untreated control HB4a-Ras cells, and the number of dorsal stress fibres was decreased in the PDT-treated populations. E-Cadherin distribution, which was already aberrant in HB4a-Ras cells, became even more diffuse in the PDT-treated populations, though its expression was increased in some of them. The strong migratory and invasive ability of HB4a-Ras cells in vitro was impaired in all the PDT-treated populations, with a behavior that was similar to the parental non-tumoral HB4a cells. MMP-2 and -9 metalloproteinase activities were also impaired in the PDT-treated populations. The evidence presented herein suggests that the cells surviving PDT would be less metastatic than the initial population. These findings encourage the use of PDT in combination with other treatments such as intraoperative or post-surgery therapeutic procedures. J. Cell. Biochem. 118: 464-477, 2017. © 2016 Wiley Periodicals, Inc.

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Resistance of oral cancer cells to 5‐ALA‐mediated photodynamic therapy

Rosin

Buck

Pelissari

et al. 2018

J of Cellular Biochemistry

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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 ). 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 , cyclin D1, p-mTOR Ser , and p-mTOR Ser . 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.

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Isolation and characterization of squamous carcinoma cells resistant to photodynamic therapy

Cited by 46 publications

References 44 publications

Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

Reversal of the Migratory and Invasive Phenotype of Ras-Transfected Mammary Cells by Photodynamic Therapy Treatment

Resistance of oral cancer cells to 5‐ALA‐mediated photodynamic therapy

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