【罂粟摘要】利多卡因抑制人乳腺癌细胞活力和迁移：TRPM7作为某些乳腺癌细胞株的靶点
利多卡因抑制人乳腺癌细胞活力和迁移：TRPM7作为某些乳腺癌细胞株的靶点
翻译：任文鑫 编辑：佟睿 审校：曹莹
贵州医科大学 高鸿教授课题组
局麻药利多卡因对某些癌细胞有抑制作用，但作用机制尚不清楚。类Melastatin瞬时受体电位7(TRPM7)离子通道在癌症中发挥作用，可能是利多卡因的靶点。本研究的目的是验证利多卡因通过调节TRPM7而影响乳腺癌细胞存活和迁移的假设。我们进行了几个实验来测量在利多卡因存在下的存活率、迁移和TRPM7的功能。我们的结果显示：(A)利多卡因抑制六种类型的乳腺癌细胞的活性和迁移，但效力不同；(B)TRPM7在介导利多卡因对至少四种类型的乳腺癌细胞的活性和迁移的影响中发挥作用。我们的工作有助于理解利多卡因对乳腺癌细胞的作用，并有助于指导其在乳腺肿瘤外科治疗中的潜在临床应用。
局麻药利多卡因对某些癌细胞有抑制作用，但作用机制尚不清楚。黑素样瞬时受体电位7(TRPM7)离子通道在某些肿瘤中异常表达，且可能在疾病中起一定作用。因此，我们认为利多卡因通过调节TRPM7影响乳腺癌细胞的存活和迁移。
我们用全细胞膜片钳和基于Fura-2AM的猝灭实验检测了利多卡因对TRPM7外源表达的HEK293细胞(HEK-M7)TRPM7功能的影响。我们分别采用基于Fura-2AM的猝灭实验、MTT实验和伤口愈合实验，检测了利多卡因对TRPM7表达的人乳腺癌细胞株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、野生型MDA-MB-231(WT-231)和TRPM7基因敲除MDA-MB-231(KO-231)的细胞存活率和迁移能力。
利多卡因(1-3 mM)对所有乳腺癌细胞系的存活和迁移均有抑制作用。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的功能。利多卡因优先抑制HEK-M7对WT-HEK和WT-231对KO-231的存活和迁移。
利多卡因不同程度地降低了所测试的人乳腺癌细胞系的存活率和迁移能力。TRPM7是利多卡因影响MDA-MB-231、AU565、T47D和MDA-MB-468细胞活性和迁移的潜在靶点之一。
Lidocaine Suppresses Viability and Migration of Human Breast Cancer Cells: TRPM7 as a Target for Some Breast Cancer Cell Lines
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 confifirmed 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. .
翻译：任文鑫
编辑：佟睿
审校：曹莹