Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Pathol Oncol Res. 2019 Oct;25(4):1467-1475. doi: 10.1007/s12253-018-0507-4. Epub 2018 Oct 27.
Chronic inflammation and dyslipidemia are associated with an increase in the incidence of colorectal cancer (CRC). Serum C- reactive protein (CRP) and oxidized low-density lipoprotein (oxLDL), as Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) ligands, increase during inflammation and dyslipidemia, respectively. To evaluate the effects of CRP on the expression of important genes involved in the development of CRC, the CRC cell line, LS174T, was treated with the commercial CRP. Based on the Real-time PCR data, in the presence of CRP, LOX-1, CEA, MMP1, and MMP2 mRNA expression significantly increased, compared to the control group. Moreover, in the presence of CRP, secretion, and expression of CEA in the cell lysate and conditioned media increased in a concentration-dependent manner. The results of flow cytometry showed that expression of LOX-1 receptors at the cell surface increased significantly in the presence of 10 mg/L of CRP. However, inhibition of LOX-1 receptors with a specific monoclonal antibody reduced the effects of CRP on protein/mRNA expression. In conclusion, Increased CRP level, can potentially elevate the expression of important genes in CRC by stimulating LOX-1 receptors.
慢性炎症和血脂异常与结直肠癌（CRC）发病率的增加有关。血清 C-反应蛋白（CRP）和氧化型低密度脂蛋白（oxLDL）分别在炎症和血脂异常时增加，作为凝集素样氧化型低密度脂蛋白受体-1（LOX-1）配体。为了评估 CRP 对 CRC 发展中重要基因表达的影响，用商业 CRP 处理 CRC 细胞系 LS174T。根据实时 PCR 数据，与对照组相比，CRP 存在时 LOX-1、CEA、MMP1 和 MMP2 mRNA 的表达显著增加。此外，在 CRP 的存在下，细胞裂解物和条件培养基中 CEA 的分泌和表达呈浓度依赖性增加。流式细胞术的结果表明，在存在 10mg/L CRP 的情况下，细胞表面 LOX-1 受体的表达显著增加。然而，用特异性单克隆抗体抑制 LOX-1 受体可降低 CRP 对蛋白/mRNA 表达的影响。总之，CRP 水平的升高可能通过刺激 LOX-1 受体来提高 CRC 中重要基因的表达。
