Lidocaine suppresses lung cancer metastasis by inhibiting polarisation of tumour-associated macrophages in mice.

Abstract

Tumour-associated macrophages (TAMs), which are frequently associated with cancer-related death in humans, play crucial roles in the metastasis of tumours, including lung cancer. However, whether lidocaine affects TAMs and exerts antimetastatic effects on non-small cell lung cancer remains unclear. Lung cancer cells were treated directly with lidocaine or cocultured with lidocaine-treated TAMs. The effect of lidocaine on lung cancer metastasis was assessed by performing experiments in C57BL/6 mice and BALB/c nude mice in vivo. The migration and proliferation of lung cancer cells were evaluated by wound healing, transwell, and CCK-8 assays. Furthermore, changes in macrophage polarisation were assessed via reverse transcription-quantitative polymerase chain reaction and flow cytometry analysis. Lidocaine suppressed tumour metastasis in C57BL/6 mice (P<0.01) but not in BALB/c nude mice. When macrophages were depleted by clodronate liposomes in C57BL/6 mice, the antimetastatic effect of lidocaine was abrogated. However, the antimetastatic effect of lidocaine was observed in BALB/c nude mice simultaneously injected with both lung cancer cells and TAMs (P<0.001). Lidocaine attenuated the polarisation of TAMs toward the M2b subtype (P<0.05) by inhibition of the activation of the protein kinase B/cAMP-response element binding protein pathway. Our results indicate that lidocaine attenuates tumour metastasis through modulation of M2b-polarised TAMs in non-small cell lung cancer, providing a mechanistic basis for the potential application of anaesthetics in lung cancer patients.