In addition, ATRA+PDT abolished mRNA expression of regenerating islet-derived protein 4 (REG4). A validation of the RNA-sec data by RT-qPCR revealed that ATRA+PDT elevated mRNA expression of early growth response 1 (EGR1) and strongly the stress-induced activating transcription factor 3 (ATF3), of which was confirmed on the protein level. Ingenuity Pathway Analysis (IPA) predicted the unfolded protein response (UPR), interferon (IFN) signaling and retinoic acid-mediated apoptosis signaling as strongly activated canonical pathways after ATRA+PDT compared to PDT.

We identified 1129 differentially expressed genes (DEGs) after ATRA+PDT compared to PDT. In the human colorectal adenocarcinoma cell line HT-29, the effect of ATRA+PDT on gene expression was evaluated by RNA sequencing (RNA-seq). Neither enhanced activity of alkaline phosphatase (ALP) nor increased expression of CD133 was detected after ATRA treatment indicating that the improved therapeutic effect of ATRA+PDT is independent of the differentiation state of the cancer cells. Compared to monotherapies, ATRA+PDT induced synergistic cytotoxic responses including promotion of apoptosis in colon and breast carcinoma cell lines. Herein, we propose combining short-term low-dose ATRA with fimaporfin-based photodynamic therapy (ATRA+PDT) for the improved treatment of solid cancers. However, lack of clinical success has prevented its approval for solid tumours. The vitamin A metabolite all-trans retinoic acid (ATRA tretinoin) has anticancer potential.

Oh no it red rat rar