Retrospective studies indicate that the use of regional anesthesia can reduce cancer recurrence after surgery which could be due to ranging from immune function preservation to direct molecular mechanisms. This study was to investigate the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. Cell viability, proliferation and migration of ovarian carcinoma (SKOV-3) and prostate carcinoma (PC-3) were examined following treatment with bupivacaine. Cleaved caspase 3, 8 and 9, and GSK-3β, pGSK-3βtyr216 and pGSK-3βser9 expression were assessed by immunofluorescence. FAS ligand neutralization, caspase and GSK-3 inhibitors and GSK-3β siRNA were applied to further explore underlying mechanisms. Clinically relevant concentrations of bupivacaine reduced cell viability and inhibited cellular proliferation and migration in both cell lines. Caspase 8 and 9 inhibition generated partial cell death reversal in SKOV-3, whilst only caspase 9 was effective in PC-3. Bupivacaine increased the phosphorylation of GSK-3βTyr216 in SKOV-3 but without measurable effect in PC3. GSK-3β inhibition and siRNA gene knockdown decreased bupivacaine induced cell death in SKOV-3 but not in PC3. Our data suggests that bupivacaine has direct ‘anti-cancer’ properties through the activation of intrinsic and extrinsic apoptotic pathways in ovarian cancer but only the intrinsic pathway in prostate cancer.

Cancer is a leading cause of morbidity and mortality worldwide. In light of demographic changes among other factors, it is anticipated this trend will continue. Surgical resection is the primary method of treating solid tumours. Unfortunately, even with the use of adjunct therapies, metastatic disease is a leading cause of death in people with cancer. Recent evidence suggests choice of anesthetic technique may influence cancer outcome. This review considers the latest evidence regarding local and regional anesthesia in the context of cancer biology. There is a focus on the indirect and direct mechanisms involved. An integrated approach is used such that diverse areas of research are explored; ranging from epigenetics to cell death pathways. With a better understanding of how regional anesthesia and/or local anesthetics interact with cancer cells, these techniques can be trialed and evaluated to ascertain potential clinical benefits in cancer patients. Thus far, there is insufficient evidence to warrant a change in clinical practice.