Raff Adam B, Thomas Carina N, Chuang Gary S, Avram Mathew M, Le Monica H, Anderson R Rox, Purschke Martin
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts.
Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts.
Lasers Surg Med. 2019 Jan;51(1):88-94. doi: 10.1002/lsm.23027. Epub 2018 Oct 15.
Lidocaine acts as a local anesthetic by blocking transmembrane sodium channel permeability, but also induces the synthesis of heat shock proteins and sensitizes cells to hyperthermia. A previous study reported two cases of deep focal skin ulceration at points corresponding to depot local lidocaine injection sites after treatment with non-ablative fractional resurfacing and it was hypothesized that lidocaine had focally sensitized keratinocytes to the thermal damage of laser treatment. The objective of this study was to investigate whether lidocaine potentiates hyperthermia damage to both normal and cancerous skin cells using an in vitro model.
Normal skin cell lines (fibroblasts, keratinocytes), skin cancer cell lines (melanoma, basal cell carcinoma), and a mucosal cancer cell line (cervical carcinoma) were exposed to various concentrations of lidocaine (0-0.3%) with or without hyperthermia (37°C, 42°C).
Compared to normal skin cells, we demonstrate that cancer cell lines show significantly increased cell toxicity when a moderate temperature (42°C) and low lidocaine concentrations (0.1-0.2%) are combined. The toxicity directly correlates with a higher percentage of cells in S-phase (28-57%) in the cancer cell lines compared to normal skin cell lines (13-19%; R-square 0.6752).
These results suggest that lidocaine potentiates thermal sensitivity of cell cycle active skin cells. The direct correlation between cell toxicity and S-phase cells could be harnessed to selectively treat skin and mucosal cancer cells while sparing the surrounding normal tissue. Additional research pre-clinically and clinically using several different heat sources (e.g., lasers, ultrasound, etc.) and lidocaine concentrations is needed to confirm and optimize these results. Lidocaine-enhanced hyperthermia may provide a non-invasive, alterative treatment option for highly proliferating, superficial skin, and mucosal lesions such as cancer or warts. Lasers Surg. Med. 51:88-94, 2019. © 2018 Wiley Periodicals, Inc.
利多卡因通过阻断跨膜钠通道通透性发挥局部麻醉作用，但也会诱导热休克蛋白的合成并使细胞对热疗敏感。先前的一项研究报告了两例在非剥脱性分次激光换肤治疗后，与局部注射利多卡因储存部位相对应的皮肤深层局灶性溃疡病例，并推测利多卡因使角质形成细胞对局灶性激光治疗热损伤敏感。本研究的目的是使用体外模型研究利多卡因是否会增强热疗对正常和癌细胞皮肤细胞的损伤。
将正常皮肤细胞系（成纤维细胞、角质形成细胞）、皮肤癌细胞系（黑色素瘤、基底细胞癌）和黏膜癌细胞系（宫颈癌）暴露于不同浓度的利多卡因（0 - 0.3%），并进行或不进行热疗（37°C、42°C）。
与正常皮肤细胞相比，我们证明当适度温度（42°C）和低利多卡因浓度（0.1 - 0.2%）联合使用时，癌细胞系显示出显著增加的细胞毒性。与正常皮肤细胞系（13 - 19%；决定系数0.6752）相比，癌细胞系中S期细胞的更高百分比（28 - 57%）与毒性直接相关。
这些结果表明利多卡因增强了细胞周期活跃的皮肤细胞的热敏感性。细胞毒性与S期细胞之间的直接相关性可用于选择性治疗皮肤和黏膜癌细胞，同时保留周围正常组织。需要在临床前和临床使用几种不同的热源（如激光、超声等）和利多卡因浓度进行进一步研究，以确认和优化这些结果。利多卡因增强的热疗可能为高度增殖的浅表皮肤和黏膜病变（如癌症或疣）提供一种非侵入性的替代治疗选择。《激光外科与医学》51:88 - 94, 2019。© 2018威利期刊公司
