Combined treatment of human colorectal tumor cell lines with chemotherapeutic agents and ionizing irradiation can in vitro induce tumor cell death forms with immunogenic potential

作者: Benjamin Frey , Christina Stache , Yvonne Rubner , Nina Werthmöller , Kathrin Schulz

DOI: 10.3109/1547691X.2012.693547

关键词: Colorectal cancerCancer researchImmunologyTumor microenvironmentNecrosisNecroptosisProgrammed cell deathCellPropidium iodideApoptosisBiology

摘要: Chemotherapeutic agents (CT) and ionizing radiation (X-ray) induce DNA damage primarily aim to stop the proliferation of tumor cells. However, multimodal anti-cancer therapies should finally result in cell death and, best, induction systemic anti-tumor immunity. Since distinct therapy-induced forms may create an immune activating microenvironment, this study examined whether sole treatment with CT that are used therapy for colorectal cancer or combination X-ray immunogenic potential. 5-Fluorouracil (5-FU), Oxaliplatin (Oxp), Irinotecan (Irino) were all potent inhibitors colony formation. This then AnnexinA5-FITC/Propidium Iodide staining. Necrosis was prominent form induced by and/or X-ray. While only a Irino leads already 1 day after treatment, also combinations Oxp 5-FU alone resulted high necrosis rates at later time points treatment. Inhibition apoptosis increased amount necrotic cells, suggesting programmed can be + plus most effective increasing expression RIP, IRF-5, p53, proteins involved apoptotic pathways. All treatments further release danger signals high-mobility group box (HMGB1) heat shock protein 70 (HSP70). The supernatants treated cells maturation dendritic It is, therefore, concluded is capable inducing vitro tumors

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