Cancers, Vol. 11, Pages 1414: Effects of Lidocaine and Src Inhibition on Metastasis in a Murine Model of Breast Cancer Surgery

Cancers, Vol. 11, Pages 1414: Effects of Lidocaine and Src Inhibition on Metastasis in a Murine Model of Breast Cancer Surgery Cancers doi: 10.3390/cancers11101414 Authors: Thomas P. Wall Peter D. Crowley Aislinn Sherwin Andrew G. Foley Donal J. Buggy Breast cancer recurs in 20% of patients following intended curative resection. In vitro data indicates that amide local anaesthetics, including lidocaine, inhibit cancer cell metastasis by inhibiting the tyrosine kinase enzyme Src. In a murine breast cancer surgery model, systemic lidocaine reduces postoperative pulmonary metastases. We investigated whether the additional administration of bosutinib (a known Src inhibitor) influences lidocaine’s observed beneficial effect in this in vivo model. Female BALB/c mice (n = 95) were inoculated with 25,000 4T1 cells into the mammary fad pad and after 7 days the resulting tumours were excised under sevoflurane anaesthesia. Experimental animals were randomized to one of four treatments administered intravenously prior to excision: lidocaine, bosutinib, both lidocaine and bosutinib in combination, or saline. Animals were euthanized 14 days post-surgery and lung and liver metastatic colonies were evaluated. Post-mortem serum was analysed for MMP-2 and MMP-9, pro-metastatic enzymes whose expression is influenced by the Src pathway. Lidocaine reduced lung, but not liver metastatic colonies versus sevoflurane alone (p = 0.041), but bosutinib alone had no metastas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research