Feng Xuesong, Ma Guangyuan, Shi Hailong, Wang Yuewen, Chao Xu
Basic Medical Academy, Shaanxi University of Chinese Medicine, Xianyang, China.
The Research Department, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, China.
Front Pharmacol. 2020 Oct 2;11:01261. doi: 10.3389/fphar.2020.01261. eCollection 2020.
The herb (Maxim) (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.
该草药（Maxim）（葫芦科），中文名为土贝母（TBM），作为辅助疗法已显示出对多种癌症的治疗效果。因此，我们旨在研究其对人肝细胞癌（HCC）的作用，并了解其背后的药理机制。在本研究中，采用了一种基于血清药理学的综合方法，将血清药理学与生物信息学预测相结合。首先，我们使用经土贝母水提物灌胃的大鼠血清培养肝癌细胞系BEL-7404，并检测其抗肿瘤作用。其次，使用ETCM数据库预测土贝母的潜在靶点，并从OMIM数据库收集已知的鼻咽癌治疗靶点。然后，使用DAVID和STRING数据库构建土贝母-肝癌潜在靶点网络。第三，基于拓扑分析和通路富集分析获得关键基因靶点。通过蛋白质免疫印迹法验证了4个代表性关键靶点的表达。结果，鉴定出36个土贝母靶点和26个已知的肝癌治疗靶点。发现这些关键靶点经常参与13条KEGG通路和4个生物学过程。四个代表性关键靶点TP53、CASP3、BCL2和BAX的表达进一步支持了土贝母对肝癌的抑制作用。总体而言，我们的研究显示了土贝母对肝癌的治疗效果。通过使用这种综合方法，我们可能找到新的潜在治疗靶点，以土贝母作为辅助疗法抑制肝癌。这也有助于我们理解肝癌对土贝母治疗反应的机制。
