Anti-tumor effects of cryptotanshinone (C19H20O3) in human osteosarcoma cell lines
Anti-tumor effects of cryptotanshinone (C19H20O3) in human osteosarcoma cell lines
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DOI：
10.1016/j.biopha.2022.112993
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发表时间：
2022-06-01
影响因子：
7.5
通讯作者：
Wilson-Robles, Heather M.
中科院分区：
文献类型：
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作者：
Vundavilli, Haswanth;Datta, Aniruddha;Wilson-Robles, Heather M.
骨肉瘤是最常见的恶性骨肿瘤，最常见于青春期和青壮年人群。尽管最近在手术和化疗方面取得了进展，但可切除转移瘤患者的总体存活率约为20%。骨肉瘤的这一挑战通常被归因于患者之间肿瘤形成特征和突变的巨大差异。对于不同的突变和多个癌基因，有必要确定既能攻击各种突变又能产生轻微副作用的治疗方法。在本文中，我们从文献中构建了骨肉瘤通路，并用常微分方程组对其进行了建模。然后，我们为每个可能的基因突变和它们的组合模拟了这个网络，并根据不同药物组合的疗效对不同的药物组合进行了排名，这些药物组合将突变的骨肉瘤网络推向细胞死亡。我们的理论结果预测，与隐丹参酮(C19H2O3)的药物组合具有最好的整体性能。具体而言，隐丹参酮与坦西罗莫司联合应用可抑制JAK/STAT、MAPK/ERK和PI3K/Akt/mTOR通路，诱导肿瘤细胞死亡。我们在SaOS2、143B、G292和HU03N1人骨肉瘤细胞系上的湿实验室实验证实了我们的理论预测，从而证明了隐丹参酮在对抗骨肉瘤方面的有效性。
Osteosarcoma is the most prevalent malignant bone tumor and occurs most commonly in the adolescent and young adult population. Despite the recent advances in surgeries and chemotherapy, the overall survival in patients with resectable metastases is around 20%. This challenge in osteosarcoma is often attributed to the drastic differences in the tumorigenic profiles and mutations among patients. With diverse mutations and multiple oncogenes, it is necessary to identify the therapies that can attack various mutations and simultaneously have minor side-effects. In this paper, we constructed the osteosarcoma pathway from literature and modeled it using ordinary differential equations. We then simulated this network for every possible gene mutation and their combinations and ranked different drug combinations based on their efficacy to drive a mutated osteosarcoma network towards cell death. Our theoretical results predict that drug combinations with Cryptotanshinone (C19H20O3), a traditional Chinese herb derivative, have the best overall performance. Specifically, Cryptotanshinone in combination with Temsirolimus inhibit the JAK/STAT, MAPK/ERK, and PI3K/Akt/mTOR pathways and induce cell death in tumor cells. We corroborated our theoretical predictions using wet-lab experiments on SaOS2, 143B, G292, and HU03N1 human osteosarcoma cell lines, thereby demonstrating the potency of Cryptotanshinone in fighting osteosarcoma.