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Simple Summary  The local anesthetic lidocaine suppresses some cancer cell lines but the mechanism is unclear. Melastatin-like transient receptor potential 7 (TRPM7) ion channels play a role in cancer and may be a target for lidocaine. The aim of our study is to test the hypothesis that lidocaine affects the viability and migration of breast cancer cells by regulating TRPM7. We conducted several assays to measure viability, migration, and TRPM7 function in the presence of lidocaine. Our results showed that (a) lidocaine suppresses viability and migration of six types of breast cancer cells, but with different potency; (b) TRPM7 plays a role in mediating the effects of lidocaine on viability and migration of at least four of these breast cancer cell types. Our work contributes to the understanding of the effect of lidocaine on breast cancer cells and helps guide its potential clinical application in the surgical treatment of breast tumors.    Abstract  Background: 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. Methods: 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). Results: 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. Conclusions: 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.

Lidocaine Suppresses Viability and Migration of Human Breast Cancer Cells: TRPM7 as a Target for Some Breast Cancer Cell Lines