Skrzycki Michał, Majewska Monika, Podsiad Małgorzata, Czeczot Hanna
Chair and Department of Biochemistry, Warsaw Medical University, Warszawa, Poland.
Acta Biochim Pol. 2009;56(4):663-70. Epub 2009 Nov 10.
The aim of the study was an evaluation of changes in protein level and activity of SOD isoenzymes, and the participation of AP-1 and NF-kappaB in subsequent stages of colorectal cancer development. Studies were conducted on 65 colorectal cancers. Controls were unchanged colon regions. Activity of SOD isoenzymes, lipid peroxidation level (TBARS), and protein level of SOD1, SOD2, AP-1 and NF-kappaB were determined. We found that the protein level and activity of SOD isoenzymes and protein level of AP-1 and NF-kappaB change in subsequent stages of clinical advancement of colorectal cancer, according to UICC (I-IV), and in grades of tumor cells differentiation (G(1)-G(3)). These results indicate adaptation of colorectal cancer cells to oxidative stress, and show that the observed changes of SOD activity and protein level depend on gradual progression of colorectal cancer, and suggest an impairment of processes regulated by AP-1 and NF-kappaB which are critical for tumor progression (proliferation, differentiation and apoptosis).
本研究旨在评估超氧化物歧化酶(SOD)同工酶的蛋白水平和活性变化,以及激活蛋白-1(AP-1)和核因子κB(NF-κB)在结直肠癌发展后续阶段中的作用。对65例结直肠癌进行了研究。对照组为未发生病变的结肠区域。测定了SOD同工酶的活性、脂质过氧化水平(硫代巴比妥酸反应物,TBARS)以及SOD1、SOD2、AP-1和NF-κB的蛋白水平。我们发现,根据国际抗癌联盟(UICC)分期(I-IV期)以及肿瘤细胞分化程度(G(1)-G(3)),在结直肠癌临床进展的后续阶段,SOD同工酶的蛋白水平和活性以及AP-1和NF-κB的蛋白水平会发生变化。这些结果表明结直肠癌细胞对氧化应激的适应性,显示所观察到的SOD活性和蛋白水平变化取决于结直肠癌的逐渐进展,并提示AP-1和NF-κB调控的对肿瘤进展(增殖、分化和凋亡)至关重要的过程受到损害。