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

Xiangtian Ling,1 Xinqi Ma,1 Xielan Kuang,1 Yuxiu Zou,1 Han Zhang,1 Han Tang,1 Han Du,1 Binbin Zhu,1 Hao Huang,1 Qing Xia,1 Minghao Chen,1 Danyi Mao,1 Dongli Chen,1 Huangxuan Shen,1,2 Jianhua Yan1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of China; 2Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Huangxuan Shen; Jianhua YanZhongshan Ophthalmic Center, Sun Yat-Sen University, 54 Xianlie Road, Guangzhou, 510060, People’s Republic of ChinaTel +8620-8733-5261; +8620-8733-0484Fax +8620-8733-3271Email shenhx@mail.sysu.edu.cn; yanjh2011@126.comPurpose: 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