Influence of non-volatile anesthetics on the migration behavior of the human breast cancer cell line MDA-MB-468.
BACKGROUND
Anesthetic agents are known to influence functions of the immune system. Anesthetic drugs also support cancer progression by suppressing the activity of immune cells. In breast carcinoma an increase in expression of peripheral-type benzodiazepine receptors (PBR) and the gamma aminobutyl acid (GABA) level has been discovered. Therefore, an investigation of a direct influence of GABA-A agonist propofol, GABA-A and PBR-agonist etomidate, and the local anesthetic drug lidocaine, which can also bind to the GABA-A receptor and PBR, on migration of breast carcinoma cells was performed.


METHODS
MDA-MB-468 cells were incubated with anesthetic agents using clinically relevant concentrations (propofol 3, 6, 9 mg/l, etomidate 2, 3, 4 mg/l, and lidocaine 1.25, 2.5, 5 mg/l). Locomotion was investigated in a three-dimensional collagen matrix using time-lapse video microscopy and computer-assisted cell-tracking.


RESULTS
The percentage of migrating cells (57.4+/-1.9) as well as the velocity (0.22+/-0.09 microm/min) and distance migrated (89.4+/-66.8 microm/10 h) increased in the presence of propofol in a dose-dependent manner (up to 74.4+/-7.5, 0.30+/-0.09, 143.8+/-89.1, respectively) compared with the long chain triglyceride (LCT) control. In contrast, no influence of etomidate on the number of migrating cells could be observed. The velocity and distance migrated at 3 and 4 mg/l were found to be statistically significantly enhanced. Treatment with lidocaine caused an increase in the percentage of migrating cells (up to 75.0+/-5.6) in velocity dose dependently (up to 0.33+/-0.06) and in distance migrated (up to 151.5+/-92.9).


CONCLUSIONS
These results show that different anesthetic drugs are able to modulate the migratory machinery of human breast carcinoma cells in vitro.
Institute of Immunology and Institute of Anesthesiology, University of Witten/Herdecke, Germany.
V
V
Garib
B
B
Niggemann
K S
KS
Zänker
L
L
Brandt
B S
BS
Kubens
D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology*; D000777:Anesthetics / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D018715:Microscopy, Video; D015742:Propofol / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000777:Anesthetics; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D008012:Lidocaine; D015742:Propofol; D005045:Etomidate