TY - JOUR
T1 - Antitumor effects of lidocaine on human breast cancer cells
T2 - An in vitro and in vivo experimental trial
AU - Chamaraux-Tran, Thiên Nga
AU - Mathelin, Carole
AU - Aprahamian, Marc
AU - Joshi, Girish P.
AU - Tomasetto, Catherine
AU - Diemunsch, Pierre
AU - Akladios, Cherif
N1 - Funding Information:
The Authors would like to thank Betty Heller and Corinne Wendling (IGBMC institute) for their help with the cell culture, Léa Wilhelm for the figure layouts and Marie-Christine Rio for her scientific support and discussion.
Funding Information:
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).
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Lidocaine
KW - Local anesthetics
KW - MDA-MB-231 cell line
KW - Xenograft model antitumor assays
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U2 - 10.21873/anticanres.12196
DO - 10.21873/anticanres.12196
M3 - Article
C2 - 29277761
AN - SCOPUS:85039793973
SN - 0250-7005
VL - 38
SP - 95
EP - 105
JO - Anticancer Research
JF - Anticancer Research
IS - 1
ER -