Lidocaine prevents breast cancer growth by targeting neuronatin to inhibit nerve fibers formation

Abstract

Lidocaine has been shown to inhibit the invasion and metastasis of breast cancer, but the mechanism still remains unclear. This study explored the relationship between lidocaine and circulating seeding of breast cancer cells from the perspective of nerve fiber formation. The cell lines MDA-MB-231 and 4T1 were subcutaneously inoculated in mice to simulate the tumor self-seeding by circulating cancer cells. Lidocaine was used to treat these mice and tumor growth was observed. Silver staining was performed to observe the distribution of nerve fibers in tumor-bearing tissues, and immunohistochemical analysis was performed to observe the expression levels of nerve-related proteins. The results showed that lidocaine treatment effectively inhibited tumor growth and nerve fiber formation, and down-regulated the expression levels of protein gene product 9.5, neurofilament, nerve growth factor (NGF), and neuronatin (Nnat). Overexpression NGF and Nnat both could reverse the therapeutic effects of lidocaine. These results suggest that the effect of lidocaine on inhibiting breast cancer invasion and metastasis may be achieved by targeting Nnat, regulating the production of NGFs in cancer cells, and subsequently inhibiting the formation of nerve fibers.

Lidocaine could promote the cuproptosis through up-regulating the long noncoding RNA DNMBP-AS1 in laryngeal cancer

“…Previous studies have shown that local anesthetics are toxic to multiple cancer types. Tu et al Reported that lidocaine could prevent breast cancer growth by targeting neuronatin to inhibit nerve bers formation [21]. Xu et al found that lidocaine could enhance the effects of chemotherapeutic drugs against bladder cancer [13].…”