Farzaneh Sahar, Salehipour Masoud, Tafvizi Farzaneh, Naseh Vahid
Department of Biology, Islamic Azad university of Parand Branch, Parand, Iran.
Rep Biochem Mol Biol. 2024 Oct;13(3):329-340. doi: 10.61186/rbmb.13.3.329.
Hepatocellular carcinoma is the most primitive form of liver cancer, which is related to chemo carcinogens such as thioacetamide (TAA) and tissue remodeling molecules such as Matrix metalloproteinases (MMPs). Antioxidants, like curcumin (Cur), can inhibit these factors. In this research, the effect of curcumin on the expression and activity of two MMP enzymes, MMP-14 and MMP-17, which are involved in the carcinogenesis of mice after chronic exposure to thioacetamide, is investigated.
In this study, 30 mice were divided into six groups and studied for 4 months. The first group, control; the second group, curcumin; the third group, TAA; the fourth group, TAA and curcumin simultaneously; the fifth group, first treated with TAA for 2 months and then curcumin; and finally, the sixth group, first treated with curcumin for 2 months and then TAA. Afterward, the mice were euthanized, and their liver tissues were transferred to the laboratory for analysis of gene and protein expression.
The averages of gene expression were calculated using SigmaPlot software and showed that the expression of MMP-17 and MMP-24 genes and the levels of their proteins were significantly increased by thioacetamide (**** < 0001) compared to the control group. Pathological observations indicated necrosis and dysplastic foci in the TAA group.
Considering the crucial roles of MMPs in various diseases, including hepatocellular carcinoma, the regulation of their gene expression and enzymatic activity is significant in preventing tumor progression. Compounds such as thioacetamide and polyphenols like curcumin can modulate the activity of MMP-17 and MMP-24.
肝细胞癌是肝癌最原始的形式,它与化学致癌物如硫代乙酰胺(TAA)以及组织重塑分子如基质金属蛋白酶(MMPs)有关。抗氧化剂,如姜黄素(Cur),可以抑制这些因素。在本研究中,研究了姜黄素对慢性暴露于硫代乙酰胺后参与小鼠致癌过程的两种MMP酶,即MMP - 14和MMP - 17的表达和活性的影响。
在本研究中,30只小鼠被分为六组并研究4个月。第一组为对照组;第二组为姜黄素组;第三组为TAA组;第四组为TAA和姜黄素同时处理组;第五组为先给予TAA处理2个月然后给予姜黄素组;最后,第六组为先给予姜黄素处理2个月然后给予TAA组。之后,将小鼠安乐死,并将其肝脏组织转移至实验室进行基因和蛋白质表达分析。
使用SigmaPlot软件计算基因表达平均值,结果显示与对照组相比,硫代乙酰胺使MMP - 17和MMP - 24基因的表达及其蛋白质水平显著增加(**** < 0.0001)。病理观察表明TAA组存在坏死和发育异常灶。
考虑到MMPs在包括肝细胞癌在内的各种疾病中的关键作用,调节其基因表达和酶活性对于预防肿瘤进展具有重要意义。硫代乙酰胺等化合物以及姜黄素等多酚类物质可以调节MMP - 17和MMP - 24的活性。