Lidocaine Inhibits Myoblast Cell Migration and Myogenic Differentiation Through Activation of the Notch Pathway

Drug Des Devel Ther. 2021 Mar 2:15:927-936. doi: 10.2147/DDDT.S290002. eCollection 2021.

Abstract

Purpose: To assess the cellular and molecular effects of lidocaine on muscles/myoblasts.

Methods: Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine.

Results: Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥0.08%, producing a dramatic reduction in cell viability. These ≥0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1.

Conclusion: This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.

Keywords: C2C12 cells; Notch signaling pathway; local anesthetics; myogenic differentiation; strabismus.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Lidocaine / pharmacology*
  • Mice
  • Myoblasts / drug effects*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Receptors, Notch
  • Lidocaine

Grants and funding

This work was supported by the National Natural Science Foundation of China (81670885). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.