PO-426 Gender disparity in lung adenocarcinoma susceptibility in experimental mice model

Abstract

Introduction Photodynamic therapy (PDT) is a clinically approved therapeutic procedure, which is entering the mainstream of cancer treatments. Nowadays PDT has been successfully used in the treatment of skin cancers, but the use of PDT against melanoma can be compromised due to the natural resistance mechanism of some melanoma cancer cells. Thus, the search for new photosensitizers is a relevant research goal. Bladder cancer is also an interesting target to PDT, due to easy irradiation accessibility by cystoscopy. Material and methods A375 human melanoma cells and HT1376 human bladder cancer cells were plated. The formulation of the sensitizers consisted in a 1 mg/mL solution in DMSO and the desired concentrations being achieved by successive dilutions. The sensitizers were administered in several concentrations (from 1 nM to 10 mM) and cells were incubated for 24 hour. Controls were performed on every test. Cells were washed with PBS and new drug-free medium was added. Each plate was irradiated with a fluence rate of 7.5 mW/cm2, to reach 10 J. Evaluation by MTT assay was performed 24 hour after the photodynamic treatment in order to evaluate the cytotoxic effect. Results and discussions Our previous in vitro PDT studies demonstrated that the increase of chlorins' hydrophilicity of leads to higher activity against A375 melanoma cells. Therefore, a series of novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins bearing dicarboxylic acid and monocarboxyic moieties were developed showing an interesting biological activity against the A375 and HT1376 cancer cells. Inhibition of the metabolic activity seems to be dependent on the concentration of the sensitizers used. With the experimental metabolic activity values, it was possible to calculate the concentration of the sensitizers that inhibits the proliferation of cultures in 50% (IC50). For this series of compounds, IC50 values ranged from mM to nM concentrations. Nevertheless, a new molecule with an IC50 value of 67,93 nM stood out. Conclusion The compounds tested were active against human melanocytic melanoma A375 cells and human bladder HT1376 cancer cells. MTT assay showed that the metabolic activity was inversely proportional to the concentration of the photosensitizer. Interestingly low IC50 values in the nanomolar range encourage further studies. Introduction Harnessing CD8 T cells to respond to tumorigenic antigens remains a supreme therapeutic strategy for sustained clearance of tumours and a resulting cancer-free life for patients. Efficient tumor-initiated T cell priming requires interferon-beta (IFN-b) production by dendritic cells and the expression of IFNb has been demonstrated to be dependent upon activation of the Stimulator of Interferon Genes (STING) pathway. Indeed, intratumoral delivery of nucleotide-based STING agonists induces a profound regression of established tumours in syngeneic mouse models. Material and methods Here, we describe a high-throughput screening platform for identifying non-nucleotide small molecule STING agonists. ...