Newly Published
Perioperative Medicine  |   January 2017
Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo
Author Notes
  • 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.).
  • W.X., D.-T.C., and J.-H.P. contributed equally to this work.
    W.X., D.-T.C., and J.-H.P. contributed equally to this work.×
  • Submitted for publication November 12, 2015. Accepted for publication December 28, 2016.
    Submitted for publication November 12, 2015. Accepted for publication December 28, 2016.×
  • Research Support: Supported by grant no. 81271246 from the Natural Science Foundation of China (China), grant no. 2012B031800075 from the Science and Technology Planning of Guangdong Province, China, and grant no. 20120171110096 from the Doctoral Program Foundation of State Education Ministry (China).
    Research Support: Supported by grant no. 81271246 from the Natural Science Foundation of China (China), grant no. 2012B031800075 from the Science and Technology Planning of Guangdong Province, China, and grant no. 20120171110096 from the Doctoral Program Foundation of State Education Ministry (China).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Zeng: Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, Guangdong, China 510060. zengwa@mail.sysu.edu.cn. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Gastrointestinal and Hepatic Systems / Pharmacology
Perioperative Medicine   |   January 2017
Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo
Anesthesiology Newly Published on January 26, 2017. doi:10.1097/ALN.0000000000001528
Anesthesiology Newly Published on January 26, 2017. doi:10.1097/ALN.0000000000001528
Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.