Effect of Propofol and Etomidate on the Proliferation, Cell-cycle Distribution, Apoptosis and Necrosis of Pancreatic Tumour Cells

Abstract

Background/aim: The influence of surgical interventions and anaesthesiological procedures on tumour progression was investigated as early as the 1920s. In current cancer management, the perioperative phase is increasingly being considered a vulnerable period with an increased risk of tumour cell dissemination due to medication, surgical manipulation, and immunosuppression. The extent to which narcotics administered in the perioperative setting influence the oncological outcomes of patients with pancreatic cancer is still unclear.

Materials and methods: To investigate the effect of propofol and etomidate on the proliferation, cell-cycle distribution, apoptosis, and necrosis of pancreatic tumour cells in vitro, PaTu 8988t and Panc-1 pancreatic cancer cells were treated with 0-1,000 μM propofol or etomidate for 24 h each. Cell proliferation was measured with enzyme-linked immunosorbent-bromodeoxyuridine assay. The apoptosis rate was analysed with annexin V staining and the cell-cycle distribution with flow cytometry.

Results: Propofol at 1,000 μM induced apoptosis and inhibited cell proliferation. The cell cycle showed an increased S-phase and reduced cells in the G₁-phase. At 100 μM, propofol significantly inhibited proliferation of the pancreatic cancer cell line PaTu 8988t and reduced cells in the G₂-phase in the cell cycle. Etomidate had no effects on cell-cycle distribution, proliferation, apoptosis, and necrosis at the concentrations used.

Conclusion: In this study, propofol was shown to have anticancer effects by induction of apoptosis and inhibition of cell proliferation, while etomidate did not affect pancreatic cancer cells. However, it is too early to make any recommendation for changes in clinical practice and further clinical studies are warranted to investigate the effect of anaesthetics on cancer progression.

Keywords: Propofol; apoptosis; cancer; cell-cycle distribution; etomidate; necrosis; pancreatic cancer; proliferation.

Figure 1. The effects of propofol (A) and etomidate (B) on the proliferation of the pancreatic carcinoma cell lines PaTu 8988t and PANC-1 in vitro. Cell proliferation was quantified by measuring bromodeoxyuridine (BrdU) incorporation. *Significantly different at p<0.05 compared to the untreated control.

Figure 2. Typical histogram of the cell-cycle distribution after marking the cell nuclei with propidium iodide in standard growth medium.

Figure 3. Cell-cycle distribution in PaTu 8988t (A) and PANC-1 (B) pancreatic cancer cell lines after treatment with 0 μM, 1 μM, 10 μM, 100 μM and 1,000 μM propofol for 24 h. Cell cycle was analysed by means of flow cytometry after staining with propidium iodide. *Significantly different at p<0.05 compared to the untreated control.

Figure 4. Cell-cycle distribution in PaTu 8988t (A) and PANC-1 (B) pancreatic cancer cell lines after treatment with etomidate for 24 h. The cellcycle distribution was analysed by means of flow cytometry after staining with propidium iodide.

Figure 5. Typical dot plots after double staining with annexin V and propidium iodide in standard growth medium.

Figure 6. The effects of propofol (A) and etomidate (B) on apoptosis in the pancreatic carcinoma cell lines PaTu 8988t (left) and PANC-1 (right) in vitro. For analysis of apoptosis, cancer cells were stained with annexin V. *Significantly different at p<0.05 compared to the untreated control.