Zhang Xiao-Lin, Yu Hao, Xiong You-Yi, Ma Shi-Tang, Zhao Lei, She Shi-Feng
Food and Drug College of Anhui Science and Technology University, Bengbu 233100, Anhui, China.
Int J Mol Sci. 2013 Jan 17;14(1):1940-51. doi: 10.3390/ijms14011940.
Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality rates. However, our understanding of the mechanism of liver tumorigenesis remains incomplete. We report the expression of myosin light chain kinase (MLCK) in the livers of rats with diethylnitrosamine (DENA)-induced HCC and investigated the correlation between MLCK and liver tumorigenesis by observing the expression of MLCK in a rat model of HCC. HCC was induced in rats by an intraperitoneal injection of DENA, and resveratrol-treated rats were orally administered resveratrol with 50 mg/kg body weight/day. The livers of rats were excised after 20 weeks and immersed in 10% formaldehyde prior to immunohistochemical and Western blot analyses for determining the level of MLCK expression. These analyses indicated that the MLCK expression was higher in the livers of HCC rats than in normal and resveratrol-treated rats. High level of MLCK expression was responsible for proliferation and anti-apoptotic effects. However, resveratrol down-regulated the expression of MLCK, which induced cell apoptosis and inhibited liver tumorigenesis in rats with DENA-induced HCC. Our results suggest that the over expression of MLCK may be related to the development of liver tumorigenesis.
肝细胞癌（HCC）由于其发病率不断上升和死亡率高，在全球范围内是一个严重的医疗保健问题。然而，我们对肝脏肿瘤发生机制的理解仍然不完整。我们报告了肌球蛋白轻链激酶（MLCK）在二乙基亚硝胺（DENA）诱导的肝癌大鼠肝脏中的表达，并通过观察肝癌大鼠模型中MLCK的表达来研究MLCK与肝脏肿瘤发生之间的相关性。通过腹腔注射DENA诱导大鼠发生肝癌，用白藜芦醇治疗的大鼠每天口服50mg/kg体重的白藜芦醇。20周后切除大鼠肝脏，在进行免疫组织化学和蛋白质印迹分析以确定MLCK表达水平之前，将其浸入10%甲醛中。这些分析表明，肝癌大鼠肝脏中MLCK的表达高于正常大鼠和白藜芦醇治疗的大鼠。高水平的MLCK表达导致增殖和抗凋亡作用。然而，白藜芦醇下调了MLCK的表达，从而诱导细胞凋亡并抑制DENA诱导的肝癌大鼠的肝脏肿瘤发生。我们的结果表明，MLCK的过度表达可能与肝脏肿瘤发生的发展有关。
