Wang Zhen, Mehmood Aamir, Yao Jia, Zhang Hui, Wang Li, Al-Shehri Mohammed, Kaushik Aman Chandra, Wei Dong-Qing
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China.
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Funct Integr Genomics. 2023 Mar 21;23(2):94. doi: 10.1007/s10142-023-01007-1.
Breast cancer is one of the leading causes of death in women worldwide. Initially, it develops in the epithelium of the ducts or lobules of the breast glandular tissues with limited growth and the potential to metastasize. It is a highly heterogeneous malignancy; however, the common molecular mechanisms could help identify new targeted drugs for treating its subtypes. This study uses computational drug repositioning approaches to explore fresh drug candidates for breast cancer treatment. We also implemented reversal gene expression and gene expression-based signatures to explore novel drug candidates computationally. The drug activity profiles and related gene expression changes were acquired from the DrugBank, PubChem, and LINCS databases, and then in silico drug screening, molecular dynamics (MD) simulation, replica exchange MD simulations, and simulated annealing molecular dynamics (SAMD) simulations were conducted to discover and verify the valid drug candidates. We have found that compounds like furosemide, gold, and dopamine showed significant outcomes. Furthermore, the expression of genes related to breast cancer was observed to be reversed by these shortlisted drugs. Therefore, we postulate that combining furosemide, gold, and dopamine would be a potential combination therapy measurement for breast cancer patients.
乳腺癌是全球女性主要死因之一。最初,它在乳腺腺组织的导管或小叶上皮中发生,生长有限且有转移潜力。它是一种高度异质性的恶性肿瘤;然而,常见的分子机制有助于识别治疗其亚型的新靶向药物。本研究采用计算药物重新定位方法来探索用于乳腺癌治疗的新候选药物。我们还实施了逆转基因表达和基于基因表达的特征来通过计算探索新的候选药物。从DrugBank、PubChem和LINCS数据库获取药物活性谱和相关基因表达变化,然后进行虚拟药物筛选、分子动力学(MD)模拟、复制交换MD模拟和模拟退火分子动力学(SAMD)模拟,以发现和验证有效的候选药物。我们发现速尿、金和多巴胺等化合物显示出显著效果。此外,观察到这些入围药物可逆转与乳腺癌相关的基因表达。因此,我们推测速尿、金和多巴胺联合使用将是乳腺癌患者潜在的联合治疗措施。