Ropivacaine and lidocaine inhibit proliferation of non-transformed cultured adult human fibroblasts, endothelial cells and keratinocytes.
Local anaesthetics are known to affect a variety of cell functions, many of which are involved in the inflammatory response. Local anaesthetics have also been shown to influence cell proliferation. The aim of this study was to examine the effect of two local anaesthetics (ropivacaine and lidocaine) on cell proliferation of cultured human fibroblasts, vascular endothelial cells and epithelial cells, i.e. keratinocytes, as earlier studies have not included primary human cell types. Significant inhibition of fibroblast proliferation was observed with concentrations of 50 microM ropivacaine or 100 microM lidocaine in 1% newborn calf serum and 500 microM ropivacaine or lidocaine in 10% newborn calf serum. The proliferation of endothelial cells was significantly inhibited by 1 mM ropivacaine in 5% human serum and 500 microM ropivacaine or 100 microM lidocaine in 40% human serum. Significant inhibition was not obtained with lidocaine when these cells were cultured in 5% HS. Significant inhibition of keratinocytes was obtained with 100 microM ropivacaine and 500 microM lidocaine. The effective concentrations are within the range of therapeutical concentrations in vivo and there seems to be a general correlation between the local anaesthetic potency and the inhibiting effect on cell proliferation. This suggest a mechanism by which local anaesthetics may exhibit anti-hyperproliferative effects in clinical situations.
Martinsson
T
T
Astra Pain Control, Preclinical Research & Development, Södertälje, Sweden.
Haegerstrand
A
A
Dalsgaard
C J
CJ
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology*; D000077212:Ropivacaine; D013936:Thymidine / Q000378:metabolism
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D008012:Lidocaine; D013936:Thymidine