288 Role of TGFβ1 in combination with NAC in the response of squamous cell carcinoma to photodynamic therapy

Tumor microenvironment(TME) has been in the spotlight of cancer progression last years. It is known that transforming growth factor β1(TGFβ1) produced by cancer-associated fibroblasts(CAF) implicated resistance to therapies, although its role cutaneous squamous cell carcinoma cells(cSCC) photodynamic therapy(PDT) and underlying mechanism not fully addressed yet. TGFβ1 effects are mediated through phosphorylation Smad proteins cytoplasm. Specifically, protein triggers formation a complex subsequently enters nucleus binds specific DNA sequences, modulating expression target genes therapy resistance. Related this, N-acetyl cysteine(NAC), treatment used for pulmonary fibrosis, reduce levels TME. Thus, NAC combination with PDT could improve cSCC counteracting CAF-derived TGFβ1. In this study, we aim understand implications secreted CAFs cells PDT, as well mechanisms NAC. investigated impact conditioned medium (CM) on response PDT. from patients were cultured CM, enriched TGFβ1, was treat two established human lines, A431 SCC13, before exposing them An induction observed but SCC13 cells. Data CGH-arrays, indirect immunofluorescence Western blot assays shed light molecular behind differential and, interestingly, pre-treatment prevented effect. Overall, our results highlight potential optimization point promising adjuvant agent cSCC.