Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion and NaV1.5 channel function

Metastatic breast and colon cancer cells express neonatal and adult splice variants of Na(V)1.5 voltage-activated Na+ channels (VASCs). Block of VASCs inhibits cell invasion. Local anaesthetics used during surgical tumour excision inhibit VASC activity on nociceptive neurones providing regional anaesthesia. Inhibition of VASCs on circulating metastatic cancer cells may also be beneficial during the perioperative period. However, ropivacaine, frequently used to provide analgesia during tumour resection, has not been tested on colon cancer cell VASC function or invasion. We used reverse transcription-polymerase chain reaction and sequencing to identify Na(V)1.5 variants in the SW620 metastatic colon cancer cell line. Recombinant adult and neonatal Na(V)1.5 variants were expressed in human embryonic kidney cells. Voltage-clamp recordings and invasion assays were used to examine the effects of ropivacaine on recombinant Na(V)1.5 channels and the metastatic potential of SW620 cells, respectively. SW620 cells expressed adult and neonatal Na(V)1.5 variants, which had similar steady-state inactivation profiles, but distinctive activation curves with the neonatal variant having a V-1/2 of activation 7.8 mV more depolarized than the adult variant. Ropivacaine caused a concentration-dependent block of both Na(V)1.5 variants, with IC50 values of 2.5 and 3.9 A mu M, respectively. However, the reduction in available steady-state current was selective for neonatal Na(V)1.5 channels. Ropivacaine inhibited SW620 invasion, with a potency similar to that of inhibition of Na(V)1.5 channels (3.8 A mu M). Ropivacaine is a potent inhibitor of both Na(V)1.5 channel activity and metastatic colon cancer cell invasion, which may be beneficial during surgical colon cancer excision.