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利多卡因和博舒替尼对 4T1 鼠乳腺癌细胞行为的影响。

The Effect of Lidocaine and Bosutinib on 4T1 Murine Breast Cancer Cell Behaviour .

机构信息

Department of Anesthesiology, Mater University Hospital, School of Medicine, University College Dublin, Dublin, Ireland;

EU COST Action 15204, Euro-Periscope, Brussels, Belgium.

出版信息

Anticancer Res. 2021 Jun;41(6):2835-2840. doi: 10.21873/anticanres.15064.

Abstract

BACKGROUND/AIM: Systemic lidocaine has recently emerged as a promising agent possessing numerous potentially anti-neoplastic effects. In vitro studies suggest that lidocaine may prevent metastasis by acting on the tyrosine kinase enzyme Src. Intravenous lidocaine has been reported to reduce pulmonary metastasis in vivo in a murine breast cancer model, however the beneficial effect is abolished by the Src inhibitor bosutinib. In this study we examined whether lidocaine and/or bosutinib affects 4T1 breast cancer cell activity in vitro and whether any drug interactions similar to that seen in murine models occur.

MATERIALS AND METHODS

4T1 murine breast cancer cells were exposed to lidocaine and/or bosutinib. Cell viability after 1 h of exposure was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration after 24 h of exposure was measured using the Oris™ migration assay.

RESULTS

Lidocaine and bosutinib alone or combined inhibited 4T1 cell viability and migration, but only at supratherapeutic concentrations. Bosutinib did not modulate lidocaine's effect on viability or migration at any concentration tested.

CONCLUSION

Although lidocaine may inhibit 4T1 metastasis in vivo, a direct effect on 4T1 cells is not detectable in vitro at non-toxic concentrations and unlike murine model testing, no unusual interaction with bosutinib was detected. Lidocaine's anti-metastatic properties are likely to be complex and multifactorial and difficult to replicate outside of a biological host.

摘要

背景/目的:全身性利多卡因最近作为一种具有多种潜在抗肿瘤作用的有前途的药物出现。体外研究表明,利多卡因可能通过作用于酪氨酸激酶酶Src 来预防转移。静脉内利多卡因已被报道可减少体内小鼠乳腺癌模型中的肺转移,但 Src 抑制剂博舒替尼可消除其有益作用。在这项研究中,我们研究了利多卡因和/或博舒替尼是否会影响 4T1 乳腺癌细胞在体外的活性,以及是否会发生与在小鼠模型中观察到的类似的药物相互作用。

材料和方法

将 4T1 小鼠乳腺癌细胞暴露于利多卡因和/或博舒替尼中。暴露 1 小时后,使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐 (MTT) 测定法测量细胞活力。暴露 24 小时后,使用 Oris™迁移测定法测量细胞迁移。

结果

利多卡因和博舒替尼单独或联合抑制 4T1 细胞活力和迁移,但仅在治疗浓度以上。在测试的任何浓度下,博舒替尼均未调节利多卡因对活力或迁移的作用。

结论

尽管利多卡因可能抑制体内 4T1 转移,但在非毒性浓度下在体外无法检测到对 4T1 细胞的直接作用,并且与小鼠模型测试不同,未检测到与博舒替尼的异常相互作用。利多卡因的抗转移特性可能是复杂的、多因素的,并且在生物宿主之外难以复制。

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