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

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:

• local anesthetics
• C2C12 cells
• myogenic differentiation
• strabismus
• Notch signaling pathway

Statement of Ethics

Informed consent, adhering to the tenets of the Declaration of Helsinki, was obtained from all participants or their guardians prior to the use of their samples in the study. This study was approved by the Institutional Review Board of the Zhongshan Ophthalmic Center. The Ethical Code is 2019KYPJ103.

Disclosure

The authors report no financial conflict of interest and conflicts of interest in this work.

Additional information

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.