Wenyuan Li,1,* Wenjie Gao,2,* Chen Lu,3,* Muhuo Ji,1 Yuan Yin,1 Hao Zhang,1 Cunming Liu,4 Chunzhao Yu2,3 

1Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of General Surgery, Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Chunzhao Yu, Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, People’s Republic of China, Email chunzhaoyu@njmu.edu.cn Cunming Liu, Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Email cunmingliu@njmu.edu.cn

Background: Colorectal cancer (CRC) is a significant contributor to cancer-related mortality globally. Despite the availability of treatments such as surgery, chemotherapy, and radiotherapy, these interventions are often accompanied by severe side effects and suboptimal patient outcomes. Recent studies have suggested that lidocaine, a widely used local anesthetic, may possess anti-tumor properties in various cancer types. This study aims to explore the impact of lidocaine on CRC cell lines, HCT 116 and SW480, to evaluate its potential as a therapeutic agent.
Methods: In vitro assays were conducted to assess the effect of lidocaine on the proliferation, migration, and invasion of CRC cells. The suppression of cell proliferation and induction of apoptosis were confirmed using colony formation, EdU, and TUNEL assays. RNA sequencing was performed on lidocaine-treated HCT 116 cells to identify differentially expressed genes and enriched biological pathways. A prognostic signature based on 16 genes was developed and validated using clinical data.
Results: Lidocaine significantly inhibited the proliferation, migration, and invasion of CRC cells in a dose-dependent manner. The assays confirmed that lidocaine suppressed cell proliferation and induced apoptosis. RNA sequencing revealed 8002 differentially expressed genes in lidocaine-treated HCT 116 cells, with significant enrichment of key pathways such as the estrogen signaling pathway and MAPK pathway. A prognostic signature based on 16 genes was developed and validated, providing a predictive model for patient survival. These findings suggest that lidocaine has potential as a therapeutic agent for CRC treatment, although further in vivo studies are required to clarify its mechanisms and optimize its clinical application.

Keywords: lidocaine, colorectal cancer, lasso-cox prognosis analysis, prognostic model, immunity