IEEE/ACM Trans Comput Biol Bioinform. 2022 May-Jun;19(3):1683-1693. doi: 10.1109/TCBB.2020.3037318. Epub 2022 Jun 3.
Osteosarcoma (OS) is the most common primary malignant bone tumor of both children and pet canines. Its characteristic genomic instability and complexity coupled with the dearth of knowledge about its etiology has made improvement in the current treatment difficult. We use the existing literature about the biological pathways active in OS and combine it with the current research involving natural compounds to identify new targets and design more effective drug therapies. The key components of these pathways are modeled as a Boolean network with multiple inputs and multiple outputs. The combinatorial circuit is employed to theoretically predict the efficacies of various drugs in combination with Cryptotanshinone. We show that the action of the herbal drug, Cryptotanshinone on OS cell lines induces apoptosis by increasing sensitivity to TNF-related apoptosis-inducing ligand (TRAIL) through its multi-pronged action on STAT3, DRP1 and DR5. The Boolean framework is used to detect additional drug intervention points in the pathway that could amplify the action of Cryptotanshinone.
骨肉瘤（OS）是儿童和宠物犬中最常见的原发性恶性骨肿瘤。其特征性的基因组不稳定性和复杂性，加上对其病因缺乏了解，使得目前的治疗难以得到改善。我们利用现有的关于 OS 中活跃的生物学途径的文献，并结合当前涉及天然化合物的研究，确定新的靶点并设计更有效的药物治疗方法。这些途径的关键组成部分被建模为具有多个输入和多个输出的布尔网络。组合电路用于从理论上预测各种药物与隐丹参酮联合使用的疗效。我们表明，草药药物隐丹参酮通过其对 STAT3、DRP1 和 DR5 的多管齐下的作用，增加对 TNF 相关凋亡诱导配体（TRAIL）的敏感性，从而诱导 OS 细胞系凋亡。布尔框架用于检测该途径中的其他药物干预点，这些点可以放大隐丹参酮的作用。
