Research Paper

Local anesthetic levobupivacaine induces ferroptosis and inhibits progression by up-regulating p53 in non-small cell lung cancer

Minghua Meng¹, Meiling Huang¹, Cuicui Liu¹, Jiming Wang¹, Weihua Ren², Shaomin Cui¹, Jianhua Gu¹, Jinlan Xie¹, Bin Ma¹, Guangzhu Yang¹, Shuncheng He¹

¹Department of Anesthesiology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 271199, China
²Pharmacy Department, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 271199, China

Received: November 3, 2020Accepted: February 16, 2021Published: June 27, 2021

https://doi.org/10.18632/aging.203138

Copyright: © 2021 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Non-small cell lung cancer (NSCLC) is a common malignancy with high mortality and poor prognosis. Levobupivacaine is a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of levobupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of levobupivacaine on the NSCLC progression and the underlying mechanism. Significantly, we revealed that levobupivacaine could inhibit the proliferation and induce the apoptosis of NSCLC cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. Meanwhile, the treatment of levobupivacaine enhanced the erastin-induced inhibition of cell growth of NSCLC cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells. Moreover, tumorigenicity analysis in nude mice showed that the treatment of levobupivacaine significantly repressed the tumor growth of NSCLC cells in vivo. In summary, we concluded that the local anesthetic levobupivacaine inhibits the progression and induces ferroptosis of NSCLC by up-regulating p53. Our finding provides new insights into the mechanism by which levobupivacaine attenuates the development of NSCLC. Levobupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC.