title: Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo.
abstract: Recent epidemiologic studies have focused on the potential beneficial effects of regional anesthetics, and the differences in cancer prognosis may be the result of anesthetics on cancer biologic behavior. However, the function and underlying mechanisms of lidocaine in hepatocellular carcinoma both in vitro and in vivo have been poorly studied.
  
  
  
  Human HepG2 cells were treated with lidocaine. Cell viability, colony formation, cell cycle, and apoptosis were assessed. The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. The antitumor activity of lidocaine in hepatocellular carcinoma with or without cisplatin was investigated with in vitro experiments and also with animal experiments.
  
  
  
  Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle (63.7 ± 1.7% vs. 72.4 ± 3.2%; P = 0.0143) and induced apoptosis (1.7 ± 0.3% vs. 5.0 ± 0.7%; P = 0.0009). Lidocaine may exert these functions by causing an increase in Bax protein and activated caspase-3 and a corresponding decrease in Bcl-2 protein through the extracellular signal-regulated kinase 1/2 and p38 pathways. More importantly, for the first time, xenograft experiments (n = 8 per group) indicated that lidocaine suppressed tumor development (P < 0.0001; lidocaine vs. control) and enhanced the sensitivity of cisplatin (P = 0.0008; lidocaine plus cisplatin vs. cisplatin).
  
  
  
  The authors' findings suggest that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. Furthermore, combining lidocaine with cisplatin may be a novel treatment option for hepatocellular carcinoma.
authors.affiliation: From the Department of Anesthesiology (W.X., D.-T.C., J.-H.P., Y.-H.C., Q.L., R.-F.X., W.-A.Z.) and Department of Hepatobiliary Oncology (Y.-F.Y.), Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; and Department of Anesthesiology, HuiZhou Municipal Central Hospital, Huizhou, China (Y.Y.).
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Dong-Tai
authors.initials: DT
authors.lastname: Chen
authors.forename: Jia-Hao
authors.initials: JH
authors.lastname: Pan
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Rui-Feng
authors.initials: RF
authors.lastname: Xue
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.forename: Wei-An
authors.initials: WA
authors.lastname: Zeng
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023041:Xenograft Model Antitumor Assays
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine