The effects of analgesics and local anesthetics on gene transcription mediated by NFATc2 and Sp1 in pancreatic carcinoma

Background Pancreatic adenocarcinoma is one of the most lethal cancers worldwide with very poor long-term survival. The treatment of choice next to chemotherapy or radiation treatment is surgical removal of the tumor. However, medication, surgery, and perioperative immunosuppression induce the constitutive activation of important signaling pathways and change the regulation of transcription factors, which may facilitate tumor progression and metastasis. Recent research has identified the transcription factors NFATc2 and Sp1 as key regulators in the carcinogenesis of pancreatic carcinoma. It is still unclear to what extent the transcription factors NFATc2 and Sp1 are influenced by analgesics given via peridural anesthetics or lidocaine infusions administered in perioperative settings or as postoperative pain therapy.Aims To conduct an in vitro analysis of the impact of clinically achievable dosages of ketamine, s-ketamine, metamizole, and paracetamol as well as of sufentanil, ropicavaine, and lidocaine on pancreatic carcinoma cells in dependency of NFATc2 and Sp1.Methods Analgesic stimulation and its effects on the expression of NFATc2 and Sp1 were investigated with immunoblot. Cell proliferation was measured with the ELISA BrdU assay.Results In PaTu8988t pancreatic carcinoma cells, 48h stimulation with ketamine and s-ketamine significantly inhibited proliferation and contemporaneously decreased endogen expression of NFATc2 in the nucleus. The addition of metamizole and lidocaine to PaTu8988t cells reduced proliferation after 48h.Conclusions New treatment concepts target the efficient modulation of specific signaling and transcription pathways. The extent to which drugs influence these mechanisms in vulnerable phases of pancreatic carcinoma cells needs to be investigated in future studies. The basis of novel therapeutic approaches to any disease is detailed knowledge of the carcinogenesis and profound molecular and biological understanding of the mechanisms.