scholarly journals Huanglianjiedu Decoction as an effective treatment for oral squamous cell carcinoma based on network pharmacology and experimental validation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lejun Zhang ◽  
Zhaoting Ling ◽  
Zhengqiang Hu ◽  
Guanmin Meng ◽  
Xinqiang Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Protein Kinase ◽  
Oral Squamous Cell Carcinoma ◽  
Network Pharmacology ◽  
Coptis Chinensis ◽  
Phellodendron Amurense ◽  
Scutellaria Baicalensis Georgi ◽  
Gardenia Jasminoides

Abstract Background Oral squamous cell carcinoma (OSCC) is one of malignant tumors in oral and maxillofacial region with high fatality. Huanglianjiedu Decoction (HLJDD) is a well-known traditional Chinese medicinal prescription, which consists of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis. Some clinical studies showed HLJDD had good effectiveness on OSCC, but the mechanism is unclear. Methods In this study, potential components of HLJDD and putative targets were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Combining with potential targets of OSCC searched from Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM), we drew protein–protein interaction (PPI) network by Cytoscape v3.2.0 software. After topological analysis we got core targets and further did Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we did the in vitro experiments to verify the major biological processes (cell cycle, apoptosis and proliferation) and signaling pathways (mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), protein kinase B (AKT)) on OSCC cell lines, SCC-25 and CAL-27. Results The potential component targets number of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis were 39, 93, 81and 88, respectively. Then we got 52 core targets which enriched in cell cycle, apoptosis, proliferation, MAPK activation etc. and obtained TOP30 pathways. On SCC-25 and CAL-27, HLJDD suppressed cell proliferation, induced late apoptosis and inhibited cell invasion and migration which were consistent with the results from network pharmacology analysis. Additionally, in cell cycle, we confirmed HLJDD inhibited G1 phase and arrested in S phase to reduce cell proliferation on SCC-25. In signaling pathways, HLJDD inhibited the phosphorylation of extracellular regulatory protein kinase 1/2 (ERK1/2) and NF-κB p65 (S468) on SCC-25 and CAL-27. Conclusions HLJDD played a potential therapeutic role on OSCC via inhibiting p-ERK1/2 and p-NF-κB p65 (S468). Graphical abstract

scholarly journals Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Yixiu Yu ◽  
Jiamei Niu ◽  
Xingwei Zhang ◽  
Xue Wang ◽  
Hongquan Song ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Bioinformatics Analyses ◽  
Gene Set

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

scholarly journals Aspirin is Involved in the Cell Cycle Arrest, Apoptosis, Cell Migration, and Invasion of Oral Squamous Cell Carcinoma

2018 ◽  
Vol 19 (7) ◽  
pp. 2029 ◽  
Author(s):  
Xiaoqi Zhang ◽  
Hao Feng ◽  
Ziyu Li ◽  
Jie Guo ◽  
Minqi Li
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Focal Adhesion ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Migration And Invasion ◽  
Invasion And Migration

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In China, its 5-year survival rate is roughly 50%, owing to acquired chemotherapeutic resistance and metastasis of the disease. Accumulating evidence demonstrates that aspirin (ASA) acts as a preventive or therapeutic agent in multiple cancers; however, anti-tumor activities induced by aspirin are unclear in OSCC. To investigate the possible role of aspirin in OSCC development, we first employed bioinformatics to analyze the anti-OSCC effects of aspirin. We performed a genetic oncology (GO) enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and the protein–protein interaction (PPI) network analysis by Cytoscape for differentially expressed genes (DEGs). We also evaluated the potential effects of aspirin on cell proliferation, invasion, migration, and apoptosis in two well-characterized OSCC cell lines (TCA8113 and CAL27). The bioinformatic results revealed that aspirin could inhibit proliferation by blocking the cell cycle, and could reduce migration and invasion via the PI3K-Akt and focal adhesion pathways. We found that ASA could downregulate the OSCC cell proliferation colony formation, invasion, and migration, as well as upregulate apoptosis. Furthermore, we found that ASA suppressed the activation of the focal adhesion kinase (FAK) and the phosphorylation of Akt, NF-κB, and STAT3. Overall, our data suggested that ASA may be developed as a chemopreventive agent to effectively treat OSCC.

scholarly journals Exploring the Mechanism of Scutellaria baicalensis Georgi Efficacy against Oral Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fanfan Hou ◽  
Yang Liu ◽  
YaHsin Cheng ◽  
Ni Zhang ◽  
Wenpeng Yan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Molecular Docking ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Network Pharmacology ◽  
Scutellaria Baicalensis Georgi ◽  
And Migration ◽  
Main Components ◽  
Compound Target

Background. Scutellaria baicalensis Georgi (SBG) has been widely shown to induce apoptosis and inhibit invasion and migration of various cancer cells. Increased evidence shows that SBG may be useful to treat oral squamous cell carcinoma (OSCC). However, the biological activity and possible mechanisms of SBG in the treatment of OSCC have not been fully elucidated. This study aimed to clarify the bioactive component and multitarget mechanisms of SBG against OSCC using network pharmacology and molecular docking. Methods. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to predict the active components in SBG, and putative molecular targets of SBG were identified using the Swiss Target Prediction database. OSCC-related targets were screened by GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OSCC via applying data mining techniques and topological parameters. Metascape database was utilized for Gene Ontology (GO) and pathway enrichment analysis. The potential interaction of the main components with core targets was revealed by molecular docking simulation, and for the correlation between core targets and OSCC prognosis analysis, the Kaplan–Meier Plotter online database was used. Results. There were 25 active compounds in SBG and 86 genes targeted by OSCC. A total of 141 signaling pathways were identified, and it was found that the PI3K-Akt signaling pathway may occupy core status in the anti-OSCC system. GO analysis revealed that the primary biological processes were related to apoptosis, proliferation, and migration. Molecular docking results confirmed that core targets of OSCC had a high affinity with the main compounds of SBG. Conclusion. Our study demonstrated multicomponent, multitarget, and multipathway characteristics of SBG in the treatment of OSCC and provided a foundation for further drug development research.

scholarly journals Circ_0000745 strengthens the expression of CCND1 by functioning as miR-488 sponge and interacting with HuR binding protein to facilitate the development of oral squamous cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kuangzheng Li ◽  
Xiaosheng Fan ◽  
Ziyi Yan ◽  
Jia Zhan ◽  
Fangyun Cao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Cycle Arrest ◽  
Squamous Cell ◽  
Cycle Arrest

Abstract Background The implication of circular RNAs (circRNAs) in human cancers has aroused much concern. In this study, we investigated the function of circ_0000745 and its potential functional mechanisms in oral squamous cell carcinoma (OSCC) to further understand OSCC pathogenesis. Methods The expression of circ_0000745, miR-488 and cyclin D1 (CCND1) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation capacity was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell cycle progression and cell apoptosis were determined by flow cytometry assay. The protein levels of CCND1, PCNA, Cleaved-caspase 3 and HuR were detected by western blot. Animal study was conducted to identify the role of circ_0000745 in vivo. The targeted relationship was verified by dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay. Results The expression of circ_0000745 was increased in OSCC tissues and cells. Circ_0000745 downregulation inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, as well as blocked tumor growth in vivo. MiR-488 was a target of circ_0000745, and circ_0000745 downregulation suppressed OSCC development by enriching miR-488. Besides, circ_0000745 regulated CCND1 expression by targeting miR-488. In addition, circ_0000745 regulated CCND1 expression by interacting with HuR protein. CCND1 knockdown also inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, and CCND1 overexpression recovered the inhibitory effects on OSCC cell malignant behaviors caused by circ_0000745 downregulation. Conclusions Circ_0000745 regulated the expression of CCND1 partly by acting as miR-488 sponge and interacting with HuR protein, thus promoting the progression of OSCC.

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

2019 ◽  
Vol 19 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Ling Gao ◽  
Jianwei Dong ◽  
Nanyang Zhang ◽  
Zhanxian Le ◽  
Wenhao Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cyclosporine A ◽  
Migration And Invasion ◽  
Signal Molecules ◽  
Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

scholarly journals Follicle-Stimulating Hormone Inhibits Adenosine 5′-Monophosphate-Activated Protein Kinase Activation and Promotes Cell Proliferation of Primary Granulosa Cells in Culture through an Akt-Dependent Pathway

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 929-935 ◽  
Author(s):  
Pradeep P. Kayampilly ◽  
K. M. J. Menon
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ampk Activation ◽  
Cyclin D2 ◽  
Cell Cycle Inhibitor ◽  
Dependent Pathway

FSH, acting through multiple signaling pathways, regulates the proliferation and growth of granulosa cells, which are critical for ovulation. The present study investigated whether AMP-activated protein kinase (AMPK), which controls the energy balance of the cell, plays a role in FSH-mediated increase in granulosa cell proliferation. Cells isolated from immature rat ovaries were grown in serum-free, phenol red free DMEM-F12 and were treated with FSH (50 ng/ml) for 0, 5, and 15 min. Western blot analysis showed a significant reduction in AMPK activation as observed by a reduction of phosphorylation at thr 172 in response to FSH treatment at all time points tested. FSH also reduced AMPK phosphorylation in a dose-dependent manner with maximum inhibition at 100 ng/ml. The chemical activator of AMPK (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, 0.5 mm) increased the cell cycle inhibitor p27 kip expression significantly, whereas the AMPK inhibitor (compound C, 20 μm) and FSH reduced p27kip expression significantly compared with control. FSH treatment resulted in an increase in the phosphorylation of AMPK at ser 485/491 and a reduction in thr 172 phosphorylation. Inhibition of Akt phosphorylation using Akt inhibitor VIII reversed the inhibitory effect of FSH on thr 172 phosphorylation of AMPK, whereas ERK inhibitor U0126 had no effect. These results show that FSH, through an Akt-dependent pathway, phosphorylates AMPK at ser 481/495 and inhibits its activation by reducing thr 172 phosphorylation. AMPK activation by 5-amino-imidazole-4-carboxamide-1-β-d-ribofuranoside treatment resulted in a reduction of cell cycle regulatory protein cyclin D2 mRNA expression, whereas FSH increased the expression by 2-fold. These results suggest that FSH promotes granulosa cell proliferation by increasing cyclin D2 mRNA expression and by reducing p27 kip expression by inhibiting AMPK activation through an Akt-dependent pathway. FSH stimulates granulosa cell proliferation by reducing cell cycle inhibitor p27 kip through AMP kinase inhibition.

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