Dataset Information

The investigation of a traditional Chinese medicine, Guizhi Fuling Wan (GFW) as an intravesical therapeutic agent for urothelial carcinoma of the bladder.

ABSTRACT:

Background

The high risk of recurrence faced by patients with bladder cancer has necessitated the administration of supplemental intravesical chemotherapy; however, such treatments often result in severe side effects. As a result, novel intravesical agents with enhanced efficacy and minimal toxicity are urgently required for the treatment of bladder cancer.

Methods

Guizhi Fuling Wan (GFW) is a traditional Chinese medicine shown to inhibit the growth of hepatocellular carcinoma. This study evaluated the growth inhibition of GFW using normal human urothelial cells and bladder cancer cells; the efficacy of GFW treatment was further compared with mitomycin C, epirubicin, and cisplatin. We also examined the progression of cell cycle and apoptosis in bladder cancer cells in response to GFW treatment. CCK-8 was employed to analyze cell viability and flow cytometry was used to study the cell cycle and apoptosis. The mechanisms underlying GFW-induced cell cycle arrest were determined by Western blot analysis.

Results

Our data demonstrate the potent inhibitory effect of GFW in the proliferation of bladder cancer cell lines, BFTC 905 and TSGH 8301. GFW presented relatively high selectivity with regard to cancer cells and minimal toxicity to normal urothelial cells. Our results also demonstrate that GFW interferes with cell cycle progression through the activation of CHK2 and P21 and induces apoptosis in these bladder cancer cells.

Conclusions

Our results provide experimental evidence to support GFW as a strong candidate for intravesicle chemotherapy against bladder cancer.

SUBMITTER: Lu CC

PROVIDER: S-EPMC3599278 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

The investigation of a traditional Chinese medicine, Guizhi Fuling Wan (GFW) as an intravesical therapeutic agent for urothelial carcinoma of the bladder.

Lu Chi-Chen CC Lin Mei-Yi MY Chen Syue-Yi SY Shen Cheng-Huang CH Chen Lih-Geeng LG Hsieh Hsiao-Yen HY Chan Michael W Y MW Chan Michael W Y MW Hsu Cheng-Da CD

BMC complementary and alternative medicine 20130223

<h4>Background</h4>The high risk of recurrence faced by patients with bladder cancer has necessitated the administration of supplemental intravesical chemotherapy; however, such treatments often result in severe side effects. As a result, novel intravesical agents with enhanced efficacy and minimal toxicity are urgently required for the treatment of bladder cancer.<h4>Methods</h4>Guizhi Fuling Wan (GFW) is a traditional Chinese medicine shown to inhibit the growth of hepatocellular carcinoma. Th ...[more]

PMID: 23433042

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Project description:Polycystic ovary syndrome (PCOS) is a common endocrine disease with reproductive dysfunction and metabolic disorder in women of childbearing age. Gastrointestinal microbiome contributes to PCOS through mediating insulin resistance. Guizhi Fuling Wan, Chinese herbal medicine, can treat PCOS with insulin resistance (PCOS-IR), but the underlying mechanism is not clear. The aim of this study was to characterize the exact mechanism of Guizhi Fuling Wan action and whether it is related to the regulation of intestinal flora structure. We induced PCOS-IR rat model by means of letrozole sodium carboxymethyl cellulose (CMC-na) solution combined with high-fat emulsion administration and randomly divided it into blank control group (K), model control group (M), low dose of Guizhi Fuling Wan group (D), middle dose of Guizhi Fuling Wan group (Z), high dose of Guizhi Fuling Wan group (G) and positive drug (Metformin) control group (Y). After 36 days of modeling and treatment, serum and stool samples from all rats were collected for a follow-up analysis. The data display that, compared with K group, elevated testosterone and HOMA-IR, turbulent estrous cycles and polycystic ovaries in M group, indicating the PCOS-IR rat model is successfully established. Increased fasting insulin is associated with higher inflammation(plasma TNF-α, IL-6, and HS-CPR concentration were determined) in M group, and the altered intestinal flora (compared with the K group, in M group the relative abundance of Alloprevotella was decreased significantly, while the relative abundance of Lachnospiraceae UCG-008, Lachnospiraceae NK4A136, Lactobacillus, Ruminiclostridium 9, and Ruminococcaceae UCG-003 was increased significantly) induced the secretion of inflammatory markers. On the other hand, Guizhi Fuling Wan can alleviate inflammation, improve insulin resistence: Lower inflammation decreased fasting insulin can be seen in G group compared with M group, this effect is related to the regulating effect of Guizhi Fuling Wan on intestinal flora (in G group, the relative abundance of Alloprevotella, Ruminococcaceae UCG-003, and Lachnospiraceae UCG-008 was increased significantly, compared with M group). This research demonstrates Guizhi Fuling Wan improve insulin resistance in polycystic ovary syndrome with the underlying mechanism of regulating intestinal flora to control inflammation. It would be useful to promote the therapeutic effect of Guizhi Fuling Wan on PCOS-IR.

Project description:AimThis study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification.MethodsThe related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis.ResultsA total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells' estrogen resistance via GPER/EGFR signaling pathway.ConclusionThe endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

Project description:BackgroundGuizhi Fuling Wan (GZFLW) is a widely used classical Chinese herbal formulae prescribed for the treatment of endometriosis (EMs). This study aimed to predict the key targets and mechanisms of GZFLW in the treatment of EMs by network pharmacology and molecular docking.MethodsFirstly, related compounds and targets of GZFLW were identified through the TCMSP, BATMAN-TCM and CASC database. Then, the EMs target database was built by GeneCards. The overlapping targets between GZFLW and EMs were screened out, and then data of the PPI network was obtained by the STRING Database to analyze the interrelationship of these targets. Furthermore, a topological analysis was performed to screen the hub targets. After that, molecular docking technology was used to confirm the binding degree of the main active compounds and hub targets. Finally, the DAVID database and Metascape database were used for GO and KEGG enrichment analysis.ResultsA total of 89 GZFLW compounds and 284 targets were collected. One hundred one matching targets were picked out as the correlative targets of GZFLW in treating EMs. Among these, 25 significant hub targets were recognized by the PPI network. Coincidently, molecular docking simulation indicated that the hub targets had a good bonding activity with most active compounds (69.71%). Furthermore, 116 items, including the inflammatory reaction, RNA polymerase, DNA transcription, growth factor activity, and steroid-binding, were selected by GO enrichment analysis. Moreover, the KEGG enrichment analysis results included 100 pathways focused on the AGE-RAGE pathway, HIF pathway, PI3K Akt pathway, MAPK pathway, and TP53 pathway, which exposed the potential mechanisms of GZFLW in treating EMs. Also, the MTT colorimetric assay indicated that the cell proliferation could be inhibited by GZFLW. Compared with the control group, the protein levels of P53, BAX, and caspase3 in the drug groups were all increased in Western blotting results. The results of flow cytometry showed that the percentage of apoptotic cells in the GZFLW group was significantly higher than that in the control group.ConclusionThrough the exploration of network pharmacology and molecular docking technology, GZFLW has a therapeutic effect on EMs through multi-target mechanism. This study provided a good foundation for further experimental research.

Project description:BACKGROUND:The well-known traditional Chinese herbal formula Guizhi Fuling Wan (GFW) was recently reported to improve the curative effects of chemotherapy for ovarian cancer with few clinical side effects. The present study aimed to investigate the reversal mechanism of sera derived from rats exposed to Guizhi Fuling Wan extract (GFWE) in cisplatin-resistant human ovarian cancer SKOV3/DDP cells; the proteins examined included phosphatase and tensin homolog (PTEN) and metadherin (MTDH), and the possible protein interaction between PTEN and MTDH was explored. METHODS:GFWE was administered to healthy Wistar rats, and the sera were collected after five days. The PubMed and CNKI databases were searched for literature on the bioactive blood components in the sera. The systemsDock website was used to predict potential PTEN/MTDH interactions with the compounds. RT-qPCR, western blotting, and immunofluorescence analyses were used to analyze the mRNA and protein levels of MTDH and PTEN. Laser confocal microscopy and coimmunoprecipitation (co-IP) were used to analyze the colocalization and interaction between MTDH and PTEN. RESULTS:Sixteen bioactive compounds were identified in GFWE sera after searching the PubMed and CNKI databases. The systemsDock website predicted the potential PTEN/MTDH interactions with the compounds. RT-qPCR, western blotting, and immunofluorescence analyses showed decreased MTDH expression and increased PTEN expression in the sera. Laser confocal microscopy images and coimmunoprecipitation (co-IP) analyses demonstrated that a colocalization and interaction occurred between MTDH and PTEN, and the addition of the sera changed the interaction status. CONCLUSIONS:GFWE restored sensitivity to cisplatin by inhibiting MTDH expression, inducing PTEN expression, and improving the interaction between MTDH and PTEN in SKOV3/DDP cells, and these proteins and their interaction may serve as potential targets for cancer treatment. The sera may represent a new source of anticancer compounds that could help to manage chemoresistance more efficiently and safely.

Dataset Information

The investigation of a traditional Chinese medicine, Guizhi Fuling Wan (GFW) as an intravesical therapeutic agent for urothelial carcinoma of the bladder.

Background

Methods

Results

Conclusions

Publications

The investigation of a traditional Chinese medicine, Guizhi Fuling Wan (GFW) as an intravesical therapeutic agent for urothelial carcinoma of the bladder.

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