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HPV 阳性 ME180 和 HPV 阴性 C33A 宫颈癌细胞中 EGFR 结合、活力和迁移的植物成分比较分析。

A comparative analysis of phyto-components on EGFR binding, viability, and migration in HPV positive ME180 and HPV negative C33A cervical cancer cells.

机构信息

Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India.

Centre for Cancer Research, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India.

出版信息

Med Oncol. 2023 Nov 14;40(12):357. doi: 10.1007/s12032-023-02223-2.

Abstract

A need for effective implementation of cervical cancer (CC) even in developed countries insist the urge for developing an effective drug molecule to treat CC. Previously, we showed an inverse correlation between survival of CC patients and epidermal growth factor (EGF) receptor (EGFR) levels. Newer tyrosine kinase inhibitors to treat CC are being constantly pursued. In this context, the proposed study is an attempt to perform a comparative analysis using 20 phyto-components to determine the effective lead molecule. Molecular docking was utilized to determine the comparative efficacy of 20 phyto-components in binding to EGFR. It was then validated by cell viability, mitochondrial membrane potential, apoptosis, migration, and matrix metalloproteinase (MMP-2) in human papilloma virus (HPV) positive and HPV negative CC cells using top nine phyto-components based on computational screening. Computational analysis identified nine phyto-components out of which five compounds were effective in reducing the survival, mitochondrial membrane potential, apoptosis, migration, and MMP-2 secretion. EGCG, plumbagin, quercetin, emodin, and naringenin were identified as effective molecules in attenuating CC survival, proliferation, and migration.

摘要

在发达国家,有效实施宫颈癌(CC)的需求也十分迫切,这促使人们研发出有效的治疗 CC 的药物分子。此前,我们发现 CC 患者的存活率与表皮生长因子(EGF)受体(EGFR)水平呈负相关。目前,人们正在不断探索新的酪氨酸激酶抑制剂来治疗 CC。在此背景下,本研究旨在使用 20 种植物成分进行比较分析,以确定有效的先导分子。采用分子对接的方法来确定 20 种植物成分与 EGFR 结合的相对效力。然后,基于计算筛选,使用前 9 种植物成分在 HPV 阳性和 HPV 阴性 CC 细胞中,通过细胞活力、线粒体膜电位、凋亡、迁移和基质金属蛋白酶(MMP-2)验证其有效性。计算分析从 20 种植物成分中鉴定出 9 种,其中 5 种化合物可有效降低细胞存活率、线粒体膜电位、凋亡、迁移和 MMP-2 分泌。表没食子儿茶素没食子酸酯(EGCG)、白花丹醌、槲皮素、大黄素和柚皮苷被鉴定为可有效抑制 CC 细胞存活、增殖和迁移的分子。

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