Department of Medical Biochemistry, Firat University, Medical Faculty, Elazig, Turkey.
Department of Medical Biochemistry, Firat University, Medical Faculty, Elazig, Turkey.
Biomed Pharmacother. 2018 Jun;102:221-229. doi: 10.1016/j.biopha.2018.03.066. Epub 2018 Mar 22.
Colorectal cancer (CRC) is an important cause of cancer-related deaths worldwide. Early diagnosis and treatment of CRCs are of importance for improving the survival. In the present study, we studied the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effects on tumor development incidence and angiogenesis in experimental CRC rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and two NSAIDs (celecoxib and diclofenac) were given orally as chemopreventive agents. Histopathological and immuno histochemical evaluations were performed in colorectal tissue samples, whereas angiogenesis parameters were studied in blood samples. Histopathological examination showed that adenocarcinoma (62.5%), dysplastic changes (31.25%) and inflammattory changes (6.25%) were detected in DMH group, whereas no pathological change was observed in control rats. In treatment groups, there was marked decrease in adenocarcinoma rate (30% and 10%, respectively). A significant increase was detected in MMP-2, MMP-9 levels and MMP-2/TIMP-2 ratio in DMH group as compared with controls and treatment groups. In immunohistochemical evaluations, there was an increase in intensity and extent of staining of MMP-2 and MMP-9 in DMH group as compared to controls and treatment groups. The decrease in celecoxib group was more prominent. Overall, it was concluded that NSAIDs, particularly cyclooxygenase-2 (COX-2) inhibitors, might have a protective effect on CRC development and slow down progression of tumor in a DMH-induced experimental cancer model. One of the possible mechanisms in the chemoprevention of colon cancer seems to be inhibition of angiogenesis by diclofenac and celecoxib.
结直肠癌（CRC）是全球癌症相关死亡的重要原因。早期诊断和治疗 CRC 对于提高生存率至关重要。在本研究中，我们研究了非甾体抗炎药（NSAIDs）诱导的化学预防作用对实验性 CRC 大鼠肿瘤发展发生率和血管生成的影响。1,2-二甲基肼二盐酸盐（DMH）用作致癌剂，两种 NSAIDs（塞来昔布和双氯芬酸）口服给药作为化学预防剂。对结直肠组织样本进行组织病理学和免疫组织化学评估，同时研究血液样本中的血管生成参数。组织病理学检查显示，DMH 组检测到腺癌（62.5%）、发育不良变化（31.25%）和炎症变化（6.25%），而对照组大鼠未见病理变化。在治疗组中，腺癌发生率明显下降（分别为 30%和 10%）。与对照组和治疗组相比，DMH 组 MMP-2、MMP-9 水平和 MMP-2/TIMP-2 比值显著升高。免疫组织化学评估显示，与对照组和治疗组相比，DMH 组 MMP-2 和 MMP-9 的染色强度和范围增加。塞来昔布组的下降更为明显。总体而言，研究结果表明，NSAIDs，特别是环氧化酶-2（COX-2）抑制剂，可能对 CRC 的发生具有保护作用，并在 DMH 诱导的实验性癌症模型中减缓肿瘤的进展。在结肠癌的化学预防中，一种可能的机制似乎是双氯芬酸和塞来昔布抑制血管生成。
