Autokrine IL-1β-Sekretion führt zu erhöhter NF-κB-Aktivität und zu Chemoresistenz in Pankreaskarzinomzellen in vivo

@ Background and Purpose: The pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly malignant phenotype and a profound chemoresistance. Thus, options for an effective treatment of this disease are still quite poor. In this study, it was investigated whether the autocrine secretion of interleukin-(IL-)1β is related to a chemoresistant phenotype of PDAC cells in vivo. □ Material and Methods: Human PancTul PDAC cells were inoculated subcutaneously into female SCID mice. After 10 days of outgrowth, animals were randomized and left untreated or treated with an IL-1β-RI antibody, etoposide, or a combination of both. After treatment for 14 days, tumor sizes were determined and each tumor was analyzed immunohistochemically for apoptosis (TUNEL), activated NF-KB (p65), and vascularization (CD31 staining). □ Results: The combination of IL-1β-RI antibody and etoposide led to a significantly reduced outgrowth of Panc Tu1 tumors in comparison to the monotherapies or no treatment. Accordingly, the number of apoptotic cells was significantly elevated in tumors of the combination group. After treatment with the IL-1β-RI antibody, less activated NF-KB was present in tumors compared to the control group. Moreover, tumors of the combination group showed a clearly reduced vascularization. □ Conclusion: The autocrine secretion of IL-1β contributes to a constitutively increased NF-κB activity in PDAC cells along with a chemoresistant phenotype.