The Effect of Lidocaine and Bosutinib on 4T1 Murine Breast Cancer Cell Behaviour In Vitro

Systemic lidocaine has recently emerged as a promising agent possessing numerous potentially anti-neoplastic effects. In vitro studies suggest that lidocaine may prevent metastasis by acting on the tyrosine kinase enzyme Src. Intravenous lidocaine has been reported to reduce pulmonary metastasis in vivo in a murine breast cancer model, however the beneficial effect is abolished by the Src inhibitor bosutinib. In this study we examined whether lidocaine and/or bosutinib affects 4T1 breast cancer cell activity in vitro and whether any drug interactions similar to that seen in murine models occur.

4T1 murine breast cancer cells were exposed to lidocaine and/or bosutinib. Cell viability after 1 h of exposure was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration after 24 h of exposure was measured using the Oris™ migration assay.

Lidocaine and bosutinib alone or combined inhibited 4T1 cell viability and migration, but only at supratherapeutic concentrations. Bosutinib did not modulate lidocaine's effect on viability or migration at any concentration tested.

Although lidocaine may inhibit 4T1 metastasis in vivo, a direct effect on 4T1 cells is not detectable in vitro at non-toxic concentrations and unlike murine model testing, no unusual interaction with bosutinib was detected. Lidocaine's anti-metastatic properties are likely to be complex and multifactorial and difficult to replicate outside of a biological host.