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网络药理学联合分子对接揭示了鹰嘴豆芽素A的抗骨肉瘤机制。

Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A.

作者信息

Luo Qing, Shi Xuan, Ding Jiarong, Ma Zhenzhen, Chen Xumei, Leng Yuanxiu, Zhang Xuhui, Liu Yang

机构信息

Department of Oncology Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Department of Anaesthesiology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.

出版信息

Evid Based Complement Alternat Med. 2019 Jan 6;2019:1410495. doi: 10.1155/2019/1410495. eCollection 2019.

DOI:10.1155/2019/1410495
PMID:30723510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6339762/
Abstract

BACKGROUND

As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered.

OBJECTIVE

To identify the potential therapeutic targets of biochanin A in treating osteosarcoma.

METHODS

In present study, an integrated approach including network pharmacology and molecular docking technique was conducted, which mainly comprises target prediction, network construction, gene ontology, and pathway enrichment. CCK8 test was employed to evaluate the cell viability of MG63 cells. Western-blot was used to verify the target proteins of biochanin A.

RESULTS

Ninety-six and 114 proteins were obtained as the targets of biochanin A and osteosarcoma, respectively. TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF were identified as the potential targets of biochanin A against osteosarcoma. Based on the western-blot detection, the expression of BGLAP, BAX, and ATF3 in MG63 cell line changed under the treatment of biochanin A.

CONCLUSION

Biochanin A can effectively suppress the proliferation of osteosarcoma and regulate the expression of BGLAP, BAX, and ATF3, which may act as the potential therapeutic targets of osteosarcoma.

摘要

背景

骨肉瘤作为青少年中发病率最高的恶性肿瘤,已成为肿瘤学研究中的一个主要问题。除了手术治疗外,骨肉瘤治疗的药物治疗策略是一种值得探索的有吸引力的方法。已证明染料木黄酮对多种实体瘤,包括骨肉瘤,具有抗肿瘤能力。但染料木黄酮抗骨肉瘤的确切机制仍有待发现。

目的

确定染料木黄酮治疗骨肉瘤的潜在治疗靶点。

方法

在本研究中,采用了一种包括网络药理学和分子对接技术的综合方法,主要包括靶点预测、网络构建、基因本体论和通路富集。采用CCK8试验评估MG63细胞的细胞活力。采用蛋白质免疫印迹法验证染料木黄酮的靶蛋白。

结果

分别获得96个和114个蛋白作为染料木黄酮和骨肉瘤的靶点。TP53、IGF1、JUN、BGLAP、ATM、MAPK1、ATF3、H2AFX、BAX、CDKN2A和EGF被确定为染料木黄酮抗骨肉瘤的潜在靶点。基于蛋白质免疫印迹检测,染料木黄酮处理后MG63细胞系中BGLAP、BAX和ATF3的表达发生了变化。

结论

染料木黄酮可有效抑制骨肉瘤的增殖,并调节BGLAP、BAX和ATF3的表达,它们可能是骨肉瘤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/9c7e96e8e6ec/ECAM2019-1410495.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/d8b0ac4b6670/ECAM2019-1410495.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/dca10809d7cc/ECAM2019-1410495.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/c22d5680a6ef/ECAM2019-1410495.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/bf86c5ef5ee8/ECAM2019-1410495.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/bced2c0cf076/ECAM2019-1410495.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/497dc708d03f/ECAM2019-1410495.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/50b41ec173f1/ECAM2019-1410495.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/9c7e96e8e6ec/ECAM2019-1410495.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/d8b0ac4b6670/ECAM2019-1410495.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/dca10809d7cc/ECAM2019-1410495.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/c22d5680a6ef/ECAM2019-1410495.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/bf86c5ef5ee8/ECAM2019-1410495.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/bced2c0cf076/ECAM2019-1410495.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/497dc708d03f/ECAM2019-1410495.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/50b41ec173f1/ECAM2019-1410495.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d46/6339762/9c7e96e8e6ec/ECAM2019-1410495.009.jpg

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