PDF(Pubmed)
Abstract：
In the face of recent advances in Cervical cancer (CC) treatment, therapeutic and surgical procedures for CC management are still inadequate. In the current study for the first time Andrographolide (Andro) has been explored for its multitarget therapeutic efficacy on NF-kB, COX-2, and PI3K/AKT expressions together in CC. The expression levels of NF-kB, COX-2, PI3K and PTEN in the CC patient samples, both at mRNA and protein levels have shown significant association with poor survival and increased tumor aggressiveness. The binding efficacy of Andro was investigated using molecular docking and molecular dynamic simulations, and the protein and ligand complex for NF-kB and COX-2 has shown high binding energy. Andro displayed cytotoxicity by impeding the in-vitro proliferation of CC cells. Andro significantly supressed the NF-kB, COX-2, and PI3K expression and enhanced the expression levels of PTEN at protein levels in-vitro. Andro induced apoptosis in a dose dependent manner and significantly inhibited the migration and invasion of CC cells. Andro exhibited similar activity in-vivo and suppressed the CC tumor growth in xenograft C57BL/6 mice model. The anti-tumor activity of Andro, both in-vitro and in-vivo has shown considerable downregulation of NF-kB and COX-2 and induced apoptosis through impeding the PI3K/AKT signalling pathway. These findings from the above study projects, administration of Andro as an effective alternate safe compound to curtail and impede cervical cancer progression.
摘要：
面对宫颈癌（CC）治疗的最新进展，用于CC管理的治疗和外科手术程序仍然不足。在目前的研究中，首次探索穿心莲内酯（Andro）对NF-kB的多靶点治疗效果，COX-2和PI3K/AKT在CC中一起表达。NF-kB的表达水平,CC患者样本中的COX-2、PI3K和PTEN，mRNA和蛋白水平均显示出与低生存率和肿瘤侵袭性增加显著相关.使用分子对接和分子动力学模拟研究了Andro的结合功效，NF-kB和COX-2的蛋白质和配体复合物显示出高结合能。Andro通过阻止CC细胞的体外增殖而表现出细胞毒性。Andro显著抑制NF-kB,COX-2和PI3K表达并在体外蛋白水平上增强PTEN的表达水平。Andro以剂量依赖的方式诱导细胞凋亡，并显着抑制CC细胞的迁移和侵袭。Andro在体内表现出相似的活性，并在异种移植C57BL/6小鼠模型中抑制了CC肿瘤的生长。Andro的抗肿瘤活性,体外和体内都显示出NF-kB和COX-2的显着下调，并通过阻碍PI3K/AKT信号通路诱导细胞凋亡。上述研究项目的这些发现，给予Andro作为一种有效的替代安全化合物来减少和阻止宫颈癌的进展。
