Biochemistry department, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, New Mansoura University, New Mansoura 7723730, Egypt.
Environ Toxicol Pharmacol. 2022 Oct;95:103943. doi: 10.1016/j.etap.2022.103943. Epub 2022 Aug 5.
Colorectal cancer (CRC) is a common malignancy with high mortality and poor prognosis. Diacerein (DIA) is an anti-inflammatory used for treatment of osteoarthritis. We delineated some underlying molecular mechanisms of DIA's anti-carcinogenic effect in CRC using in vivo and in vitro models. Human Caco-2 cells were treated with DIA followed by MTT and Annexin V assays and CRC was experimentally induced using 1,2-dimethylhydrazine. DIA (50 mg/kg/day, orally) was administrated for 8 weeks. The MTT assay confirmed cytotoxic effect of DIA in vitro and Annexin V confirmed its apoptotic effect. DIA resulted in regression of tumour lesions with reduced colonic TLR4, NF-κB and TNF-α protein levels and down-regulated VEGF expression, confirming anti-angiogenic impact. DIA triggered caspase-3 expression and regulated Wnt/β-Catenin pathway, by apparently interrupting the IL-6/STAT3/ lncRNA HOTAIR axis. In conclusion, DIA disrupted IL-6/STAT3/ lncRNA HOTAIR axis which could offer an effective therapeutic strategy for the management of CRC.
结直肠癌（CRC）是一种死亡率和预后不良的常见恶性肿瘤。双醋瑞因（DIA）是一种用于治疗骨关节炎的抗炎药。我们使用体内和体外模型描绘了 DIA 在 CRC 中的抗癌作用的一些潜在分子机制。用人结肠癌细胞（Caco-2 细胞）用 DIA 处理，然后进行 MTT 和 Annexin V 检测，并用 1,2-二甲基肼实验性诱导 CRC。DIA（50mg/kg/天，口服）给药 8 周。MTT 检测证实了 DIA 的体外细胞毒性作用，Annexin V 证实了其凋亡作用。DIA 导致肿瘤病变消退，结肠 TLR4、NF-κB 和 TNF-α 蛋白水平降低，VEGF 表达下调，证实了其抗血管生成作用。DIA 触发了 caspase-3 的表达，并调节了 Wnt/β-Catenin 通路，明显打断了 IL-6/STAT3/lncRNA HOTAIR 轴。总之，DIA 破坏了 IL-6/STAT3/lncRNA HOTAIR 轴，为 CRC 的治疗提供了一种有效的治疗策略。
