The Effects of Analgesics on the Migration of Pancreatic Cancer Cells

Abstract

Background/aim: Adenocarcinoma of the pancreas is one of the most aggressive malignant diseases in humans. Characteristics of this tumour type are poor response to radiotherapy and chemotherapeutic agents as well as metastasis in the absence of an organ capsule. The best therapeutic option is surgical removal of the tumour followed by chemotherapy or radiotherapy. Yet, even after surgical R0-resection, the 5-year survival probability is only about 20% because of the high recurrence rate of this tumour and complications due to metastases. Furthermore, recent studies have shown that the perioperative period is a particularly vulnerable phase, during which tumour progression and metastasis may be facilitated. The effects of analgesics administered during the perioperative period are still unknown. The present work investigated the effects of analgesics on pancreatic cancer cell migration in vitro.

Materials and methods: The migratory potential of pancreatic cancer cells was analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semi-permeable membrane under different stimuli. Cell concentration was measured by reading fluorescence (Ex/Em=530/590 nm) in a plate reader.

Results: Migration in PANC-1 pancreatic cancer cells was significantly decreased after 24 h stimulation with 100 μM of ropivacaine, 100 nM of sufentanil, 1,000 μM of ropivacaine and 1,000 nM of sufentanil. In the PaTu 8988t cell line, incubation with 10 μM of ropivacaine caused a slight but statistically significant increase in migration, whereas lidocaine, metamizole and paracetamol did not significantly affect migration.

Conclusion: The risk of tumour progression and metastasis seems to be increased during major oncological surgical interventions. The recent advances in the molecular and biological understanding of pathogenesis of pancreatic cancer have not yet significantly improved patient outcome. Therefore, further studies are needed to identify the underlying mechanisms of this aggressive tumour and establish new therapeutic options for the future.

Keywords: Migration; analgesics; cancer; lidocaine; metamizole; pancreatic cancer; paracetamol; ropivacaine; sufentanil.

Figure 1. The effects of metamizole and paracetamol on cell migration in PaTu 8988t (a) and PANC-1 (b) pancreatic cancer cells in vitro. Cell migration was quantified by using a Boyden chamber in which cells migrate through a semi-permeable membrane under different stimuli. *Statistical significance at p<0.05 compared to untreated controls.

Figure 2. The effects of lidocaine, ropivacaine and sufentanil and the combination of ropivacaine and sufentanil on migration in PaTu 8988t (a) and PANC-1 (b) pancreatic cancer cells in vitro. The cell migration rate was detected by using a Boyden chamber in which cells migrate through a semi-permeable membrane under different stimuli. *Statistical significance at p<0.05 compared to untreated controls.