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

D. T. Baptista-Hon, F. M. Robertson, G. B. Robertson, S. J. Owen, G. W. Rogers, E. L. Lydon, N. H. Lee, T. G. Hales (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    Background Metastatic breast and colon cancer cells express neonatal and adult splice variants of NaV1.5 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.

    Methods We used reverse transcription–polymerase chain reaction and sequencing to identify NaV1.5 variants in the SW620 metastatic colon cancer cell line. Recombinant adult and neonatal NaV1.5 variants were expressed in human embryonic kidney cells. Voltage-clamp recordings and invasion assays were used to examine the effects of ropivacaine on recombinant NaV1.5 channels and the metastatic potential of SW620 cells, respectively.

    Results SW620 cells expressed adult and neonatal NaV1.5 variants, which had similar steady-state inactivation profiles, but distinctive activation curves with the neonatal variant having a V1/2 of activation 7.8 mV more depolarized than the adult variant. Ropivacaine caused a concentration-dependent block of both NaV1.5 variants, with IC50 values of 2.5 and 3.9 µM, respectively. However, the reduction in available steady-state current was selective for neonatal NaV1.5 channels. Ropivacaine inhibited SW620 invasion, with a potency similar to that of inhibition of NaV1.5 channels (3.8 µM).

    Conclusions Ropivacaine is a potent inhibitor of both NaV1.5 channel activity and metastatic colon cancer cell invasion, which may be beneficial during surgical colon cancer excision.
    Original languageEnglish
    Pages (from-to)i39-i48
    Number of pages10
    JournalBritish Journal of Anaesthesia
    Volume113
    Issue numberSuppl. 1
    DOIs
    Publication statusPublished - Jul 2014

    Keywords

    • Adult
    • Age Factors
    • Amides
    • Anesthetics, Local
    • Cell Movement
    • Collagen
    • Colonic Neoplasms
    • Dose-Response Relationship, Drug
    • Drug Combinations
    • Electrophysiological Phenomena
    • Humans
    • Infant, Newborn
    • Laminin
    • Lidocaine
    • NAV1.5 Voltage-Gated Sodium Channel
    • Neoplasm Invasiveness
    • Neoplasm Metastasis
    • Neoplasm Proteins
    • Patch-Clamp Techniques
    • Proteoglycans

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