LIDOCAINE OPPOSES MORPHINE-INDUCED VEGF SECRETION BY PROSTATE CANCER CELLS
The ability of tumors to grow and metastasize is enhanced by neoangiogenesis, a process by which tumors become vascularized via inducing the branching of existing vessels towards them. Tumors do so by producing vascular endothelial growth factor (VEGF) that mobilizes endothelial cells to produce new vessels. Morphine is an opioid drug used for pain management in patients with cancer. It is known for enhancing angiogenesis1, an effect that according to our recent studies in lung endothelial cells is opposed by the local anesthetic lidocaine2.
The aim of this study was to examine whether lidocaine demonstrates an antiagiogenic effect in a variety of prostate cancer cell lines (RWPE-1 cells RPWE-2, NB11/NB-14 and WPE1 – NB-26-65), that are mimicking various stages of prostate cancer progression from early pre-metastatic stage (RWPE-1, RPWE-2) to metastatic stage (WPE1-NB-26-65), by opposing morphine-induced VEGF secretion
Materials and Methods
Human tumorigenic prostate epithelial cell lines derived from RWPE-1 cells were used for the experiments. Cells were platted on 6 well-dishes and left undisturbed until reaching 75% confluency. VEGF secretion was measured using a dot-blot system. The effect of morphine and lidocaine at a concentration of 10 μM each, as well as their combined effect on VEGF secretion from the above cells lines was measured. For studies of angiogenic potential a Boyden chamber transwell system was used with the prostate cancer cells seeded at the bottom of the well and human microvascular endothelial cells platted on the insert. Co-cultured cells were left undisturbed and endothelial cells migrating towards the cancerous epithelial layer were detected using Crystal Violet staining.
The pro-angiogenic effects of morphine are stage dependent being highest on cells representing prostate carcinoma in situ that are characterized by high basal VEGF secretion .
Lidocaine may be suppressing the morphine angiogenic potential in some prostate cancer types by decreasing the morphine induced production of VEGF.
Lidocaine infusions may acquire a distinct clinical application in the perioperative care of prostate cancer patients treated with morphine for pain control.
2) Votta-Velis G., et al. Do Local Anesthetics Attenuate Morphine-induced angiogenesis? If so what is the mechanism? Best of meeting Abstract Award 39th Annual Regional Anesthesiology and Acute Pain Medicine meeting Chicago 3.-6.04.2014