Dataset Information

Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGF?-Induced EMT in Ovarian Cancer.

ABSTRACT: The compound fuling granule (CFG) is a traditional Chinese drug which has been used to treat ovarian cancer in China for over twenty years. Nevertheless, the underlying molecular mechanism of its anti-cancer effect remains unclear. In this study, microarray data analysis was performed to search differentially expressed genes in CFG-treated ovarian cancer cells. Several cell cycle and epithelial-mesenchymal transition (EMT) related genes were identified. The microarray analyses also revealed that CFG potentially regulates EMT in ovarian cancer. We also found that, functionally, CFG significantly suppresses ovarian cancer cell proliferation by cell cycle arrest, apoptosis and senescence and the AKT/GSK-3? pathway is possibly involved. Additionally, the invasion and migration ability of ovarian cancer induced by TGF? is significantly suppressed by CFG. In conclusion, our results demonstrated that CFG suppresses ovarian cancer cell proliferation as well as TGF?1-induced EMT in vitro. Finally, we discovered that CFG suppresses tumor growth and distant metastasis in vivo. Overall, these findings provide helpful clues to design novel clinical treatments against cancer.

SUBMITTER: Tao F

PROVIDER: S-EPMC5201296 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFβ-Induced EMT in Ovarian Cancer.

Tao Fangfang F Ruan Shanming S Liu Wenhong W Wang Libin L Xiong Yang Y Shen Minhe M

PloS one 20161230 12

The compound fuling granule (CFG) is a traditional Chinese drug which has been used to treat ovarian cancer in China for over twenty years. Nevertheless, the underlying molecular mechanism of its anti-cancer effect remains unclear. In this study, microarray data analysis was performed to search differentially expressed genes in CFG-treated ovarian cancer cells. Several cell cycle and epithelial-mesenchymal transition (EMT) related genes were identified. The microarray analyses also revealed that ...[more]

PMID: 28036353

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Project description:BackgroundCompound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets.MethodsSignificant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of CFG were analyzed by LC-MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug-likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein-protein interaction network was prepared using STRING. The ingredient-target network was established using Cytoscape. Molecular docking was performed to visualize the molecule-protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK-8 assay, wound-scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells.ResultsA total of 56 bioactive ingredients of CFG and 185 CFG-OC-related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S-transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin-dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways (P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo. DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells.ConclusionBased on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation.

Dataset Information

Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGF?-Induced EMT in Ovarian Cancer.

Publications

Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFβ-Induced EMT in Ovarian Cancer.

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