Abstract
BackgroundAdenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression. Particularly during this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Therefore, the effects of metamizole and paracetamol on tumor progression should be investigated in more detail because the extent to which these substances influence the carcinogenesis of pancreatic carcinoma is still unclear. This study analyzed the influence of metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic cancer cell lines PaTu 8988t and Panc-1 in vitro.MethodsCell proliferation was measured by means of the ELISA BrdU assay and the rate of apoptosis by flow cytometry using the Annexin V assay.ResultsMetamizole and paracetamol significantly inhibited cell proliferation in pancreatic cancer cells. After the addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced after 3 h of incubation but significantly increased after 9 h of incubation.ConclusionThe oncogenic potential of pancreatic adenocarcinoma is mainly characterized by its extreme growth rate. Non-opioid analgesics such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. The combination of metamizole or paracetamol with cytotoxic therapeutic approaches may achieve synergistic effects. Further studies are necessary to identify the underlying mechanisms so that new therapeutic options may be developed for the treatment of this aggressive tumor.
Highlights
Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body
Cell proliferation behavior The pancreatic cancer cell lines PaTu 8988t and Panc-1 were either stimulated with 1–500 μM of metamizole (a), 1–500 μM of MAA (b), 1–1000 μM of paracetamol (c), or 250 of μM metamizole, and 250 μM of paracetamol (d) for 48 h
Proliferation was significantly inhibited in the PaTu 8988t cell line after incubation with 1–500 μM of metamizole (Fig. 1a) and 1–1000 μM of paracetamol (Fig. 1c)
Summary
Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression During this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Malsy et al BMC Pharmacology and Toxicology (2017) 18:77 system, and drug therapy increases the risk of tumor dissemination, exerting a negative impact on disease progression in oncological patients [7, 8]. At this vulnerable stage, substances such as metamizole and paracetamol are administered as anesthetics or postoperative analgesics [9, 10]. The direct effects of these substances on the tumor progression and carcinogenesis of pancreatic carcinoma are still unclear and require further investigations
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