Chamaraux-Tran Thiên-Nga, Mathelin Carole, Aprahamian Marc, Joshi Girish P, Tomasetto Catherine, Diemunsch Pierre, Akladios Cherif
Department of Anesthesiology and Surgical Intensive Care, Hautepierre Hospital, CHRU, University Hospital of Strasbourg, Strasbourg, France
Functional Genomics and Cancer Department, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France.
Anticancer Res. 2018 Jan;38(1):95-105. doi: 10.21873/anticanres.12196.
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.
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.
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.
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.
回顾性研究表明区域麻醉对癌症手术后复发具有保护作用。但缺乏体内抗肿瘤作用的确证。我们检测了利多卡因对各种乳腺癌细胞系的体外抗肿瘤作用,然后在体内以临床相关浓度评估了这些特性。
体外实验:将正常乳腺上皮细胞(NBEC)MCF-10A和三种肿瘤乳腺上皮细胞(TBEC)系(MCF-7腔面A型、MDA-MB-231三阴性和SKBr3 HER2阳性)暴露于浓度递增的利多卡因中。通过MTT、伤口愈合和软琼脂生长试验评估细胞活力、迁移和非锚定依赖性生长。体内实验:给6周龄的重度联合免疫缺陷小鼠腹腔注射MDA-MB-231细胞,并用腹腔内利多卡因或磷酸盐缓冲盐水治疗。当小鼠达到实验终点时实施安乐死,或处死以确定腹膜癌指数和总体肿瘤体积。
利多卡因降低了所有细胞系的活力,与NBEC相比抑制了TBEC的迁移,并损害了三阴性细胞的非锚定依赖性生长。腹腔内注射利多卡因使用与当前临床镇痛设置一致的剂量,提高了患有MDA-MB-231腹膜癌小鼠的存活率。
与局部麻醉可能对癌症治疗有益的观点一致,在实验研究中利多卡因对乳腺癌细胞具有保护作用。然而,局部麻醉药对乳腺癌的有益影响需要通过额外的临床前和临床试验来强化。