Gopcevic K, Rovcanin B, Kekic D, Krivokapic Z, Dragutinovic V
Institute of Chemistry in Medicine, Clinical Centre of Serbia.
Centre for Endocrine Surgery, Clinical Centre of Serbia.
Folia Biol (Praha). 2017;63(5-6):190-196. doi: 10.14712/fb2017063050190.
Matrix metalloproteinases (MMPs) are involved in tumour invasion and metastasis of colorectal carcinoma. Oxidative stress represents one of the possible mechanisms that activate inactive MMPs. Oxidative stress increases lipid peroxidation, which causes impaired membrane permeability and leakage of lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) into circulation. Our aim was to assess the activity of MMP-2 and MMP-9 and its relation to the parameters of oxidative stress and membrane damage markers in patients with different TNM (tumour, lymph nodes, metastasis) stages of colorectal carcinoma. MMP-2 and -9 activities were evaluated by gelatin zymography. Oxidative stress was examined by quantifying serum malondialdehyde (MDA) concentration. LDH and MDH activities were determined spectrophotometrically. The activities of MMP-2 and -9 were significantly higher in the sera of colorectal carcinoma patients when compared to healthy subjects. There was a stage-dependent increase in relative MMP-2 activity compared to the overall serum gelatinolytic activity. The activity of MMP-9 was the highest in TNM III. The MDA concentration and the LDH and MDH activities were significantly higher in colorectal carcinoma patients than in controls, while LDH and MDH activities were stage dependent. There was significant correlation between serum MMP-2 and LDH activity in TNM II, III and IV patients. A stage-dependent increase of LDH and MDH activity was observed. We highlight here that MMP-9 could be a 100% sensitive marker of TNM stage III of colorectal carcinogenesis. In this study it was shown for the first time that gelatinolytic activity in colorectal carcinoma is associated with redox imbalance.
基质金属蛋白酶（MMPs）参与结直肠癌的肿瘤侵袭和转移。氧化应激是激活无活性MMPs的可能机制之一。氧化应激会增加脂质过氧化，导致膜通透性受损以及乳酸脱氢酶（LDH）和苹果酸脱氢酶（MDH）泄漏到循环中。我们的目的是评估不同TNM（肿瘤、淋巴结、转移）分期的结直肠癌患者中MMP-2和MMP-9的活性及其与氧化应激参数和膜损伤标志物的关系。通过明胶酶谱法评估MMP-2和-9的活性。通过定量血清丙二醛（MDA）浓度来检测氧化应激。用分光光度法测定LDH和MDH的活性。与健康受试者相比，结直肠癌患者血清中MMP-2和-9的活性显著更高。与总体血清明胶酶解活性相比，MMP-2的相对活性呈分期依赖性增加。MMP-9的活性在TNM III期最高。结直肠癌患者的MDA浓度以及LDH和MDH的活性显著高于对照组，而LDH和MDH的活性具有分期依赖性。在TNM II、III和IV期患者中，血清MMP-2和LDH活性之间存在显著相关性。观察到LDH和MDH活性呈分期依赖性增加。我们在此强调，MMP-9可能是结直肠癌发生TNM III期的100%敏感标志物。在本研究中首次表明，结直肠癌中的明胶酶解活性与氧化还原失衡有关。
