Abstract
Aim: Retrospective studies have suggested a protective effect of regional anesthesia against recurrence after cancer surgery. But confirmation of the in vivo antitumor effects is lacking. We examined the in vitro antitumor effects of lidocaine on various breast cancer cell lines and then assessed these properties in vivo at clinically relevant concentrations. Materials and Methods: In vitro experiments: normal breast epithelial cells (NBEC) MCF-10A and three tumor breast epithelial cells (TBEC) lines (MCF-7 luminal A, MDA-MB-231 triple-negative and SKBr3 HER2 positive) were exposed to increasing concentrations of lidocaine. Cell viability, migration and anchorage-independent growth were assessed by MTT, wound healing, and soft-agar growth assays. In vivo experiments: 6-week-old severe combined immunodeficient mice were injected intraperitoneally with MDA-MB-231 cells and were treated with intraperitoneal lidocaine or phosphate-buffered saline. The mice were euthanized when they reached experimental endpoints or sacrificed to determine peritoneal carcinomatosis index and global tumor volumes. Results: Lidocaine reduced the viability of all the cell lines, inhibited migration of TBEC compared to the NBEC, and compromised the anchorage-independent growth of the triple-negative cells. Intraperitoneal lidocaine improved survival of mice with MDA-MB-231 peritoneal carcinomatosis using doses that are consistent with the current clinical settings for analgesia. Conclusion: In agreement with the notion that local anesthesia may be beneficial for cancer therapy, lidocaine has a protective effect against breast cancer cells in experimental studies. However, the beneficial impact of local anesthetics on breast cancer needs to be strengthened by additional preclinical and clinical trials.
Footnotes
Funding
This study was funded by the grant ANR-10-LABX-0030-INRT, a French State fund managed by the Agence Nationale de la Recherche under the frame program “Investissements d'Avenir” labelled ANR-10-IDEX-0002-02. Thiên-Nga Chamaraux-Tran is an IGBMC International Ph.D. Program fellow supported by LabEx INRT funds. The Authors declare receiving funds from the charity Seins et Vie and the Société Française d'Anesthésie-Réanimation (SFAR).
Conflict of Interest
G.P. Joshi is a consultant for Pacira, Baxter, Mallincrodt and Merck Pharmaceuticals. The others Authors declare that they have no conflict of interest in regard to this study.
Ethical Approval
All applicable international, national, and institutional guidelines for the care and use of animals were followed. All animal experiments were carried out according to the revised European Community directive (2010/63/EU, September 24, 2010) on the protection of animals used for scientific purposes and with an ethical agreement (no. 38.2012.01.046) according to the French transposition of the European Community directive. This article does not include any studies with human participants performed by any of the Authors.
Presentation
Preliminary data for this study were presented as a poster presentation at the 2014 and 2015 American Society of Anesthesiologists Annual Meeting, and as oral communication at the 2014 and 2015 French Society of Anesthesia and Intensive Care Annual Congress.
- Received October 4, 2017.
- Revision received October 29, 2017.
- Accepted November 1, 2017.
- Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved