Rasool Mahmood, Malik Arif, Ghuman Ahmad Ashar, Ashraf Muhammad Abdul Basit, Arooj Mahwish, Waquar Sulayman, Zahid Sara, Shaheen Sumera, Qazi Aamer, Naseer Muhammad Imran, Zamzami Mazin A, Al-Ghafari Ayat, Baothman Othman A, Zeyadi Mustafa, Helmi Nawal, Choudhry Hani, Jamal Mohammad Sarwar, Al-Qahtani Mohammed Hussein
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.
Front Oncol. 2018 Jun 7;8:205. doi: 10.3389/fonc.2018.00205. eCollection 2018.
Colorectal cancer (CRC) is the third most common type of cancer and leading cause of death worldwide. Major risk factors involved in the development of CRC are increased dietary sources, genetics, and increasing age. Purpose of the study was to find the role of different variables in the progression of CRC.
50 blood samples from CRC patients and 20 samples from control were collected. Serum was separated from the blood by centrifugation. This serum was assessed for several antioxidants like superoxide dismutase (SOD), glutathione, glutathione peroxidase, glutathione reductase, catalase, vitamin A, C, and E, and pro-oxidants such as malondialdehyde, advanced oxidation protein products (AOPPs), and AGEs according to their respective protocols. Matrix metalloproteinase-7 (MMP-7) and isoprostanes were assessed by ELISA kits.
Lower levels of GSH (4.86 ± 0.78 vs 9.65 ± 1.13 μg/dl), SOD (0.08 ± 0.012 vs 0.46 ± 0.017 μg/dl), CAT (2.45 ± 0.03 vs 4.22 ± 0.19 μmol/mol of protein), and GRx (5.16 ± 0.06 vs 7.23 ± 0.36 μmol/ml) in the diseased group were recorded as compared with control. Higher levels of GPx (6.64 ± 0.19 mmol/dl) were observed in the subjects in comparison with control group (1.58 ± 0.30 mmol/dl). Highly significant decreased levels of vitamin A (0.81 ± 0.07 vs 2.37 ± 0.15 mg/ml), vitamin E (15.42 ± 1.26 vs 25.96 ± 2.19 mg/ml), and vitamin C (47.67 ± 7.69 vs 80.37 ± 10.21 mg/ml) were observed in the patients in contrast to control group. The reversal of antioxidants in later stages of CRC may be due to compensatory mechanisms in cancerous cells. The levels of MDA (nmol/ml) were also assessed, which shows significantly increased level in CRC patients as compared with control groups (3.67 ± 0.19 vs 1.31 ± 0.27). The levels of protein oxidation products [AGEs (2.74 ± 0.16 vs 0.84 ± 0.05 IU) and AOPPs (1.32 ± 0.02 vs 0.82 ± 0.07 ng/ml)] were significantly increased in subjects as compared with control. The levels of MMP-7 (64.75 ± 3.03 vs 50.61 ± 4.09 ng/ml) and isoprostanes (0.71 ± 0.03 vs 0.16 ± 0.02 ng/ml) were also analyzed. This shows that the levels of isoprostanes increased due to high lipid peroxidation mediate higher levels of MMP-7, which promotes development of CRC.
Following study suggested that elevated oxidative and inflammatory status along with lipid peroxidation and matrix metalloproteinases are the chief contributors in the progression of CRC.
结直肠癌（CRC）是全球第三大常见癌症类型及主要死因。CRC发生的主要风险因素包括饮食来源增加、遗传因素和年龄增长。本研究的目的是找出不同变量在CRC进展中的作用。
收集50例CRC患者的血样和20例对照样本。通过离心从血液中分离出血清。根据各自的方案对该血清进行多种抗氧化剂如超氧化物歧化酶（SOD）、谷胱甘肽、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、过氧化氢酶、维生素A、C和E以及促氧化剂如丙二醛、晚期氧化蛋白产物（AOPPs）和晚期糖基化终产物（AGEs）的评估。使用ELISA试剂盒评估基质金属蛋白酶-7（MMP-7）和异前列腺素。
与对照组相比，患病组的谷胱甘肽（GSH）水平较低（4.86±0.78 vs 9.65±1.13μg/dl）、SOD水平较低（0.08±0.012 vs 0.46±0.017μg/dl）、过氧化氢酶（CAT）水平较低（2.45±0.03 vs 4.22±0.19μmol/mol蛋白）和谷胱甘肽还原酶（GRx）水平较低（5.16±0.06 vs 7.23±0.36μmol/ml）。与对照组相比，受试者的谷胱甘肽过氧化物酶（GPx）水平较高（6.64±0.19 mmol/dl）。与对照组相比，患者体内维生素A（0.81±0.07 vs 2.37±0.15 mg/ml）、维生素E（15.42±1.26 vs 25.96±2.19 mg/ml）和维生素C（47.67±7.69 vs 80.37±10.21 mg/ml）的水平显著降低。CRC后期抗氧化剂的逆转可能是由于癌细胞中的代偿机制。还评估了丙二醛（MDA）（nmol/ml）水平，结果显示CRC患者的MDA水平与对照组相比显著升高（3.67±0.19 vs 1.31±0.27）。与对照组相比，受试者体内蛋白质氧化产物[AGEs（2.74±0.16 vs 0.84±0.05 IU）和AOPPs（1.32±0.02 vs 0.82±0.07 ng/ml）]的水平显著升高。还分析了MMP-7（64.75±3.03 vs 50.61±4.09 ng/ml）和异前列腺素（0.71±0.03 vs 0.16±0.02 ng/ml）的水平。这表明由于高脂质过氧化导致异前列腺素水平升高，进而介导更高水平的MMP-7，促进了CRC的发展。
以下研究表明，氧化和炎症状态升高以及脂质过氧化和基质金属蛋白酶是CRC进展的主要促成因素。
