An Integrative Serum Pharmacology-Based Approach to Study the Anti-Tumor Activity of B. paniculatum Aqueous Bulb Extract on the Human Hepatocellular Carcinoma Cell Line BEL-7404.

An Integrative Serum Pharmacology-Based Approach to Study the Anti-Tumor Activity of B. paniculatum Aqueous Bulb Extract on the Human Hepatocellular Carcinoma Cell Line BEL-7404.
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基于综合血清药理学的方法研究 B.paniculatum 球茎水提取物对人肝癌细胞系 BEL-7404 的抗肿瘤活性

DOI:
10.3389/fphar.2020.01261
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发表时间:
2020
影响因子:
5.6
通讯作者:
Chao X
Chao X
中科院分区:
医学2区
文献类型:
--
作者:
Feng X;Ma G;Shi H;Wang Y;Chao X

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土贝母(Bolbostemma paniculatum(Maxim)Franquet)是葫芦科植物土贝母(Bolbostemma paniculatum(Maxim)Franquet)的一种重要药用植物,具有抗肿瘤、抗癌的作用。本研究采用血清药理学和生物信息学相结合的方法,从血清药理学的角度,探讨其对人肝细胞癌(HCC)的治疗作用及其药理学机制。首先,我们用TBM水提液灌胃给药的大鼠血清培养肝癌细胞株BEL-7404,检测其抗肿瘤作用。其次,使用ETCM数据库预测TBM推定靶点,并从OMIM数据库中收集已知的NPC治疗靶点。利用大卫和STRING数据库构建了TBM-HCC推定靶点网络。第三,基于拓扑分析和途径富集分析,获得关键基因靶点。通过Western blotting验证了4个代表性关键靶点的表达。结果,确定了36个TBM靶点和26个已知的HCC治疗靶点。发现这些关键靶点经常参与13个KEGG通路和4个生物过程。四个代表性关键靶点:TP 53、CASP 3、BCL 2和BAX的表达进一步支持TBM对HCC的抑制。总之,我们的研究显示了TBM对HCC的疗效。通过使用这种整合的方法,我们可能会发现新的潜在的治疗靶点,以抑制肝癌使用TBM作为一种连续治疗。它也可以帮助我们了解HCC治疗对TBM的反应机制。
The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.
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