Jurj Ancuta, Tomuleasa Ciprian, Tat Tiberiu T, Berindan-Neagoe Ioana, Vesa Stefan V, Ionescu Daniela C
Research Center for Functional Genomic, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Research Center for Functional Genomic, Biomedicine and Translational Medicine;Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
J Gastrointestin Liver Dis. 2017 Mar;26(1):45-50. doi: 10.15403/jgld.2014.1121.261.juj.
It is now well documented that certain anesthetic techniques may influence long term outcome in cancer patients undergoing surgery. More recently, local anesthetics proved certain antiproliferative effects in cancer cells. In our study, we aimed to investigate if lidocaine has antiproliferative effects in human hepatocarcinoma cells and to identify possible mechanisms of these effects.
We investigated the inhibitory effect of different concentrations of lidocaine on the proliferation of cultured HepG2 human hepatocarcinoma cells and LX2 normal liver fibroblasts. Cells were exposed to nine different concentrations of lidocaine for 72h. MTT assay was used to investigate HepG2 and LX2 proliferation while Western blotting was used for detection of p53 expression level.
Our data showed that lidocaine inhibited cell proliferation in a concentration-dependent manner in both HepG2 and LX2. The antiproliferative effects of lidocaine in LX2 were significantly diminished as compared with those in HepG2 (p< 0.001). Similarly, the expression level of p53 was significant decreased in HepG2 lines treated with lidocaine as compared with control and LX2 (p = 0.0241).
In clinically relevant concentrations, lidocaine had significant antiproliferative effects on human hepatocarcinoma cells. These effects were time and dose-dependent. One of the possible mechanisms of these effects is by modifying the P53 expression level. The relevance of these findings in clinical practice is limited; clinical impact of these effects on the outcome of patients with hepatocarcinoma undergoing surgery or minimal invasive procedures needs to be demonstrated in future animal models and clinical studies.
现已充分证明，某些麻醉技术可能会影响接受手术的癌症患者的长期预后。最近，局部麻醉药在癌细胞中显示出一定的抗增殖作用。在我们的研究中，我们旨在研究利多卡因是否对人肝癌细胞具有抗增殖作用，并确定这些作用的可能机制。
我们研究了不同浓度的利多卡因对培养的HepG2人肝癌细胞和LX2正常肝成纤维细胞增殖的抑制作用。将细胞暴露于九种不同浓度的利多卡因中72小时。采用MTT法检测HepG2和LX2细胞的增殖情况，同时采用蛋白质印迹法检测p53表达水平。
我们的数据显示，利多卡因在HepG2和LX2细胞中均以浓度依赖性方式抑制细胞增殖。与HepG2细胞相比，利多卡因对LX2细胞的抗增殖作用明显减弱（p<0.001）。同样，与对照组和LX2细胞相比，用利多卡因处理的HepG2细胞系中p53的表达水平显著降低（p = 0.0241）。
在临床相关浓度下，利多卡因对人肝癌细胞具有显著的抗增殖作用。这些作用具有时间和剂量依赖性。这些作用的可能机制之一是通过改变P53表达水平。这些发现在临床实践中的相关性有限；这些作用对接受手术或微创手术的肝癌患者预后的临床影响需要在未来的动物模型和临床研究中得到证实。
