CONICET | Buscador de Institutos y Recursos Humanos

Photodynamic therapy (PDT) is a non-thermal technique for inducing tumor damage following administration of a light-activated photosensitizingdrug (PS). In a previous work we found that PDT induces cytoskeleton changes in HB4a-Ras cells (human mammary breast carcinoma HB4a cellstransfectedwith the RAS oncogene). In the present workwe have studied themigratory and invasive features and the expression of proteins relatedto 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), andMerocyanine 540 (MC).Aslight (1.25- to 2-fold) degree of resistancewas acquired in cell populationssubjected to the three successive PDT treatments. However, complete cell killing was achieved after a light dose increase. Regardless of the PSemployed, all the PDT-treated populations had shorter stress fibres than the untreated controlHB4a-Ras cells, and the number of dorsal stressfibreswas decreased in the PDT-treated populations. E-Cadherin distribution,whichwas already aberrant in HB4a-Ras cells, became evenmore diffuse inthe PDT-treated populations, though its expression was increased in some of them. The strong migratory and invasive ability of HB4a-Ras cells invitro was impaired in all the PDT-treated populations, with a behavior that was similar to the parental non-tumoral HB4a cells. MMP-2 and -9metalloproteinase activitieswere also impaired in the PDT-treated populations. The evidence presented herein suggests that the cells surviving PDTwould be less metastatic than the initial population. These findings encourage the use of PDT in combination with other treatments such asintraoperative or post-surgery therapeutic procedures

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