Wen Gang, Xin Naixing
Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
Transl Cancer Res. 2021 Nov;10(11):4817-4828. doi: 10.21037/tcr-21-1937.
Breast cancer, as one of the most common malignant tumors in women, is still a great threat to women all over the world. Dexmetomidine (DMED) is a highly selective α2-adrenergic receptor agonist, which has attracted much attention in recent years. This study aimed to clarify the potential mechanism of DMED in regulating the activity of breast cancer cells.
Breast cancer cell lines MCF-7 and MDA-MB-231 were treated with DMED. The levels of miR-199a and HIF-1α mRNA were detected using quantitative real-time polymerase chain reaction (QRT-PCR); the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and transwell assays were applied to monitor the activity of breast cancer cells; the apoptosis of breast cancer cells was detected using the caspase-3 activity assay and flow cytometry; binding of miR-199a and HIF-1α was assessed using double luciferase reporter gene assay, and western blot was employed to monitor the level of HIF-1α in cells.
The cytotoxicity and apoptosis of MCF-7 and MDA-MB-231 cells was inhibited by DMED. It also downregulated the expression of miR-199a in breast cancer cells and enhanced the downregulation of miR-199a to promote the activity of breast cancer cells and inhibit apoptosis. Also, miR-199a targeted HIF-1α. Further functional experiments confirmed that DMED promoted the progression of breast cancer through the miR-199a/HIF-1α axis.
DMED promotes the activity of breast cancer cells through miR-199a/HIF-1αaxis. This can provide some reference for DMED in the clinical treatment of breast cancer.
乳腺癌作为女性最常见的恶性肿瘤之一，仍然对全球女性构成巨大威胁。右美托咪定（DMED）是一种高度选择性的α2 - 肾上腺素能受体激动剂，近年来备受关注。本研究旨在阐明DMED调节乳腺癌细胞活性的潜在机制。
用DMED处理乳腺癌细胞系MCF - 7和MDA - MB - 231。采用定量实时聚合酶链反应（QRT - PCR）检测miR - 199a和HIF - 1α mRNA水平；应用3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基 - 2H - 四唑溴盐（MTT）法和Transwell实验监测乳腺癌细胞活性；使用caspase - 3活性检测和流式细胞术检测乳腺癌细胞凋亡；采用双荧光素酶报告基因检测评估miR - 199a与HIF - 1α的结合，并通过蛋白质免疫印迹法监测细胞中HIF - 1α的水平。
DMED抑制了MCF - 7和MDA - MB - 231细胞的细胞毒性和凋亡。它还下调了乳腺癌细胞中miR - 199a的表达，并增强了miR - 199a的下调以促进乳腺癌细胞活性并抑制凋亡。此外，miR - 199a靶向HIF - 1α。进一步的功能实验证实，DMED通过miR - 199a/HIF - 1α轴促进乳腺癌进展。
DMED通过miR - 199a/HIF - 1α轴促进乳腺癌细胞活性。这可为DMED在乳腺癌临床治疗中提供一些参考。
