Jiang Yuan, Gou Hui, Zhu Jiang, Tian Si, Yu Lehua
Department of Rehabilitation Medicine and Physical Therapy, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.
Department of Rehabilitation Medicine and Physical Therapy, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Oncol Lett. 2016 Aug;12(2):1164-1170. doi: 10.3892/ol.2016.4709. Epub 2016 Jun 13.
It is well known that local anesthetics have a broad spectrum of pharmacological actions, acting as nerve blocks, and treating pain and cardiac arrhythmias via blocking of the sodium channel. The use of local anesthetics could reduce the possibility of cancer metastasis and recurrence following surgical tumor excision. The purpose of the present study was to investigate the inhibitory effect of lidocaine upon the invasion and migration of transient receptor potential cation channel subfamily V member 6 (TRPV6)-expressing cancer cells. Human breast cancer MDA-MB-231 cells, prostatic cancer PC-3 cells and ovarian cancer ES-2 cells were treated with lidocaine. Cell viability was quantitatively determined by MTT assay. The migration of the cells was evaluated using the wound healing assay, and the invasion of the cells was assessed using a Transwell assay. Calcium (Ca) measurements were performed using a Fluo-3 AM fluorescence kit. The expression of TRPV6 mRNA and protein in the cells was determined by quantitative-polymerase chain reaction and western blot analysis, respectively. The results suggested that lidocaine inhibits the cell invasion and migration of MDA-MB-231, PC-3 and ES-2 cells at lower than clinical concentrations. The inhibitory effect of lidocaine on TRPV6-expressing cancer cells was associated with a reduced rate of calcium influx, and could occur partly as a result of the downregulation of TRPV6 expression. The use of appropriate local anesthetics may confer potential benefits in clinical practice for the treatment of patients with TRPV6-expressing cancer.
众所周知,局部麻醉药具有广泛的药理作用,可作为神经阻滞剂,并通过阻断钠通道来治疗疼痛和心律失常。使用局部麻醉药可降低手术切除肿瘤后癌症转移和复发的可能性。本研究的目的是探讨利多卡因对表达瞬时受体电位阳离子通道亚家族V成员6(TRPV6)的癌细胞侵袭和迁移的抑制作用。用人乳腺癌MDA-MB-231细胞、前列腺癌PC-3细胞和卵巢癌ES-2细胞进行利多卡因处理。通过MTT法定量测定细胞活力。使用伤口愈合试验评估细胞的迁移情况,并使用Transwell试验评估细胞的侵袭情况。使用Fluo-3 AM荧光试剂盒进行钙(Ca)测量。分别通过定量聚合酶链反应和蛋白质印迹分析测定细胞中TRPV6 mRNA和蛋白质的表达。结果表明,利多卡因在低于临床浓度时可抑制MDA-MB-231、PC-3和ES-2细胞的侵袭和迁移。利多卡因对表达TRPV6的癌细胞的抑制作用与钙内流速率降低有关,并且可能部分是由于TRPV6表达下调所致。在临床实践中,使用适当的局部麻醉药可能对治疗表达TRPV6的癌症患者具有潜在益处。