Department of Spleen and Stomach Diseases, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region 530023, P.R. China.
Research Department, The Affiliated Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Mol Med Rep. 2019 May;19(5):4256-4270. doi: 10.3892/mmr.2019.10062. Epub 2019 Mar 19.
Cinobufotalin is a chemical compound extracted from the skin of dried bufo toads that may have curative potential for certain malignancies through different mechanisms; however, these mechanisms remain unexplored in breast cancer. The aim of the present study was to investigate the antitumor mechanism of cinobufotalin in breast cancer by using microarray data and in silico analysis. The microarray data set GSE85871, in which cinobufotalin exerted influences on the MCF‑7 breast cancer cells, was acquired from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were analyzed. Subsequently, protein interaction analysis was conducted, which clarified the clinical significance of core genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze cinobufotalin‑related pathways. The Connectivity Map (CMAP) database was used to select existing compounds that exhibited curative properties similar to those of cinobufotalin. A total of 1,237 DEGs were identified from breast cancer cells that were treated with cinobufotalin. Two core genes, SRC proto‑oncogene non‑receptor tyrosine kinase and cyclin‑dependent kinase inhibitor 2A, were identified as serving a vital role in the onset and development of breast cancer, and their expression levels were markedly reduced following cinobufotalin treatment as detected by the microarray of GSE85871. It also was revealed that the 'neuroactive ligand‑receptor interaction' and 'calcium signaling' pathways may be crucial for cinobufotalin to perform its functions in breast cancer. Conducting a matching search in CMAP, miconazole and cinobufotalin were indicated to possessed similar molecular mechanisms. In conclusion, cinobufotalin may serve as an effective compound for the treatment of a subtype of breast cancer that is triple positive for the presence of estrogen, progesterone and human epidermal growth factor receptor‑2 receptors, and its mechanism may be related to different pathways. In addition, cinobufotalin is likely to exert its antitumor influences in a similar way as miconazole in MCF‑7 cells.
华蟾素是从干燥蟾蜍皮中提取的一种化合物，通过不同的机制可能对某些恶性肿瘤具有治疗潜力；然而，这些机制在乳腺癌中尚未得到探索。本研究旨在通过微阵列数据和计算机分析研究华蟾素在乳腺癌中的抗肿瘤机制。从基因表达综合数据库中获取了 GSE85871 微阵列数据集，其中华蟾素对 MCF-7 乳腺癌细胞有影响，并对差异表达基因（DEGs）进行了分析。随后，进行了蛋白质相互作用分析，阐明了核心基因的临床意义，并用基因本体论和京都基因与基因组百科全书分析了华蟾素相关途径。连接映射（CMAP）数据库用于选择具有与华蟾素相似治疗特性的现有化合物。从用华蟾素处理的乳腺癌细胞中鉴定出 1237 个 DEGs。两个核心基因 SRC 原癌基因非受体酪氨酸激酶和周期蛋白依赖性激酶抑制剂 2A，被鉴定为在乳腺癌的发生和发展中起重要作用，并且它们的表达水平在 GSE85871 的微阵列中明显降低。还表明“神经活性配体-受体相互作用”和“钙信号”途径可能对华蟾素在乳腺癌中发挥作用至关重要。在 CMAP 中进行匹配搜索表明，咪康唑和华蟾素具有相似的分子机制。总之，华蟾素可能是一种有效的治疗雌激素、孕激素和人表皮生长因子受体-2 受体三重阳性的乳腺癌亚型的化合物，其机制可能与不同的途径有关。此外，华蟾素可能在 MCF-7 细胞中以类似于咪康唑的方式发挥其抗肿瘤作用。
