Liu Hengrui, Dilger James P, Lin Jun
Department of Anesthesiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.
Cancers (Basel). 2021 Jan 10;13(2):234. doi: 10.3390/cancers13020234.
The local anesthetic lidocaine suppresses some cancer cell lines but the mechanism is unclear. The melastatin-like transient receptor potential 7 (TRPM7) ion channel is aberrantly expressed in some cancers and may play a role in the disease. Hence, we suggested that lidocaine affects the viability and migration of breast cancer cells by regulating TRPM7.
We measured the effects of lidocaine on TRPM7 function in HEK293 with exogenous TRPM7 expression (HEK-M7) using whole-cell patch-clamp and fura-2AM-based quench assay. We measured the effect of lidocaine on TRPM7 function, cell viability, and migration in TRPM7 expressing human breast cancer cell lines using fura-2AM-based quench, MTT, and wound-healing assays respectively. We compared cell viability and migration of wild type HEK293 cells (WT-HEK) with HEK-M7 and wild type MDA-MB-231 (WT-231) with TRPM7 knockout MDA-MB-231 (KO-231).
Lidocaine (1-3 mM) inhibited the viability and migration of all of these breast cancer cell lines. Functional evidence for TRPM7 was confirmed in the MDA-MB-231, AU565, T47D, and MDA-MB-468 cell lines where lidocaine at 0.3-3 mM suppressed the TRPM7 function. Lidocaine preferentially suppressed viability and migration of HEK-M7 over WT-HEK and WT-231 over KO-231.
Lidocaine differentially reduced the viability and migration of human breast cancer cell lines tested. TRPM7 is one of the potential targets for the effects of lidocaine on viability and migration in MDA-MB-231, AU565, T47D, and MDA-MB-468.
局部麻醉药利多卡因可抑制某些癌细胞系，但其机制尚不清楚。类褪黑素瞬时受体电位7（TRPM7）离子通道在某些癌症中异常表达，可能在该疾病中起作用。因此，我们推测利多卡因通过调节TRPM7影响乳腺癌细胞的活力和迁移。
我们使用全细胞膜片钳和基于fura-2AM的淬灭测定法，测量利多卡因对具有外源性TRPM7表达的HEK293（HEK-M7）中TRPM7功能的影响。我们分别使用基于fura-2AM的淬灭、MTT和伤口愈合测定法，测量利多卡因对表达TRPM7的人乳腺癌细胞系中TRPM7功能、细胞活力和迁移的影响。我们比较了野生型HEK293细胞（WT-HEK）与HEK-M7以及野生型MDA-MB-231（WT-231）与TRPM7敲除的MDA-MB-231（KO-231）的细胞活力和迁移情况。
利多卡因（1-3 mM）抑制了所有这些乳腺癌细胞系的活力和迁移。在MDA-MB-231、AU565、T47D和MDA-MB-468细胞系中证实了TRPM7的功能证据，其中0.3-3 mM的利多卡因抑制了TRPM7功能。利多卡因优先抑制HEK-M7的活力和迁移，而不是WT-HEK，优先抑制WT-231的活力和迁移，而不是KO-231。
利多卡因差异性地降低了所测试的人乳腺癌细胞系的活力和迁移。TRPM7是利多卡因影响MDA-MB-231、AU565、T47D和MDA-MB-468细胞活力和迁移的潜在靶点之一。
