Abstract
With the widespread use of lidocaine for pain control in cancer therapy, its antitumor activity has attracted considerable attention in recent years. This paper provides a simple strategy of combining lidocaine with chemotherapy drugs for cancer therapy, aiming to relieve chemotherapy-induced pain and achieve stronger antitumor efficacy. However, there is still a lack of substantial pre-clinical evidence for the efficacy and related mechanisms of such combinations, obstructing their potential clinical application. In this study, we propose intraperitoneal chemotherapy (IPC) against gastric cancer (GC) as an ideal scenario to evaluate the efficacy of a lidocaine/paclitaxel combination. Firstly, we used human GC cells MKN-45-luc to investigate the antitumor activity and related mechanisms of the lidocaine/paclitaxel combination in vitro. Then, we used C57BL/6 mice with intraperitoneal drug suffusion to evaluate the efficacy of lidocaine to suppress paclitaxel-induced hyperalgesia and related mechanisms. Lastly, in BALB/c tumor-bearing nude mice we evaluated the synergistic antitumor activity and pain-relieving effect of the lidocaine/paclitaxel combination. Our results showed enhanced antitumor activity for the lidocaine/paclitaxel combination, which induced apoptosis, inhibited migration, and the invasion of GC cells in a synergistic manner. In animal models, the lidocaine/paclitaxel combination effectively inhibited growth and peritoneal metastasis of the tumor, resulting in prolonged survival time. Meanwhile, lidocaine showed considerable anti-inflammatory activity alongside its anesthetic effect, which, in combination, effectively relieved hyperalgesia induced by paclitaxel. These results suggested that intraperitoneal suffusion with lidocaine/paclitaxel could be a pain-free IPC formulation with enhanced antitumor activity, which could provide a promising treatment for GC with peritoneal metastasis.