scholarly journals Cyclocarya paliurus Polysaccharide Inhibits Glioma Cell U251 Proliferation, Migration, and Invasion and Promotes Apoptosis via the GSK3β/β-Catenin Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaolong Du ◽  
Kai Guo ◽  
Yongqian Ma ◽  
Jianyong Chang
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Cyclocarya Paliurus ◽  
Protein Levels ◽  
U251 Cells

Objective. To investigate the effects of Cyclocarya paliurus polysaccharide (CPP) on the proliferation, migration, invasion, and apoptosis of human glioma U251 cells and further explore the underlying mechanism. Methods. U251 cells were cultured in vitro and treated with various concentrations (25, 50, 75, 100, 125, and 150 μmol/L) of CPP for 24, 48, and 72 h. Cell counting kit-8 was used to detect the activity of cell proliferation. Wound-healing assay, Transwell assay, and flow cytometry were used to measure the effects of CPP on the migration, invasion, and apoptosis of U251 cells, respectively. Western blotting was used to determine the protein expression involved in the GSK3β/β-catenin signaling pathway and its downstream genes related to proliferation, migration, invasion, and apoptosis including Cyr61, CCND1, Vimentin, and Slug. Meanwhile, qRT-PCR was used to detect the mRNA levels of Cyr61, CCND1, Vimentin, and Slug. Results. We found that CPP not only could inhibit the proliferation, migration, and invasion of U251 cells but also promote its apoptosis in vitro. Besides, CPP could significantly inhibit the phosphorylation and decrease the protein levels of GSK3 β at ser9 site (p<0.05), and thus increasing the phosphorylation of β-Catenin at ser33/37 site (p<0.05), resulting in β-Catenin degradation. In addition, we also found that CPP could downregulate the mRNA (p<0.05) and protein expression (p<0.05) of downstream genes of GSK3 β/β-catenin signaling pathway including Cyr61, CCND1, Vimentin, and Slug, which are related to proliferation, migration, invasion, and apoptosis. Conclusion. CPP could inhibit the expression of GSK3β, promote the degradation of β-catenin, and downregulate the levels of GSK3β/β-catenin downstream genes including Cyr61, CCND1, Vimentin, and Slug, which regulate the proliferation, migration, invasion, and apoptosis of glioma cells.

scholarly journals Yiqi Huoxue Recipe Improves Liver Regeneration in Rats after Partial Hepatectomy via JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wen-cong Li ◽  
Su-xian Zhao ◽  
Wei-guang Ren ◽  
Hui-juan Du ◽  
Yu-guo Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Protective Effects ◽  
Jnk Pathway ◽  
Expression Levels ◽  
Protein Levels ◽  
Mrna And Protein Expression

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.

Effects and Mechanisms of Tripartite Motif Containing 14 Downregulation on Proliferation, Migration, and Invasion of Cancerous Pancreatic PANC-1 Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 402-406
Author(s):  
Huaping Gong ◽  
Long Chen ◽  
Ruipeng Dong
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Cellular Proliferation ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Sirna Transfection ◽  
Akt Phosphorylation

This study aimed to investigate the effect and mechanism of TRIM14 downregulation on the apoptosis, migration, and invasion of cancerous pancreatic PANC-1 cells. PANC-1 cells cultured in vitrowere classified to a control (normal culture), negative (neutral siRNA transfection), and siTRIM14 group (TRIM14 siRNA transfection). RT-PCR was adopted to test TRIM14 mRNA expression. Cellular proliferation was determined by CCK-8, and transwell chamber invasion and apoptosis by flow cytometry. AKT signaling pathway related proteins CyclinD1, MMP-2, Bcl-2, and AKT phosphorylation, and TRIMI14 protein expression, were determined by western blotting. Compared with the control group, TRIMI14 expression, cellular proliferation ability, infiltration, transfer AKT phosphorylation, and TRIMI14, CyclinD1, MMP-2, and Bcl-2 protein expression were greatly reduced in siTRIM14 cells, and the apoptotic ability was significantly enhanced (P < 0.05). However, no striking differences were detected between the negative and control groups (P > 0.05). Downregulating TRIM14 expression can inhibit the proliferation, invasion, and migration of PANC-1 cells, and promote apoptosis. The mechanism may be associated with the inhibition of AKT signaling pathway activation.

scholarly journals H3.3K27M Mutation Promotes The Migration and Invasion of Glioma Cells By Activating β-Catenin/USP1 Signaling

2022 ◽  
Author(s):  
Zhiyuan Sun ◽  
Yufu Zhu ◽  
Xia Feng ◽  
Xiaoyun Liu ◽  
Kunlin Zhou ◽  
...  
Keyword(s):  
Glioma Cells ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
High Grade ◽  
Protein Levels ◽  
Adult Glioma

Abstract H3.3K27M is a newly identified molecular pathology marker in glioma and is especially correlated with the malignancy of diffuse intrinsic pontine glioma (DIPG). In recent years, accumulating research has revealed that other types of glioma also contain the H3.3K27M mutation. However, the role of H3.3K27M in high-grade adult glioma, which is the most malignant glioma, has not been investigated. In this study, we focused on exploring the expression and function of H3.3K27M in high-grade adult glioma patients. We found that H3.3K27M is partly highly expressed in high-grade glioma tissues. Then, we introduced H3.3K27M into H3.3 wild-type glioma cells, U87 cells and LN229 cells. We found that H3.3K27M did not regulate the growth of glioma in vitro and in vivo; however, the survival of mice with transplanted tumors was significantly reduced. Further investigation revealed that H3.3K27M expression mainly promoted the migration and invasion of glioma cells. Moreover, we certified that H3.3K27M overexpression enhanced the protein levels of ꞵ-catenin and p-ꞵ-catenin, the protein and mRNA levels of ubiquitin-specific protease 1 (USP1), and the protein level of enhancer of zeste homolog 2 (EZH2). Importantly, the ꞵ-catenin inhibitor XAV-939 significantly attenuated the upregulation of the aforementioned proteins. Overall, the H3.3K27M mutation is present in a certain proportion of high-grade glioma patients and facilitates a poor prognosis by promoting the metastasis of glioma by regulating the ꞵ-catenin/USP1/EZH2 pathway.

scholarly journals ZBTB16 Overexpression Enhances White Adipogenesis and Induces Brown-Like Adipocyte Formation of Bovine White Intramuscular Preadipocytes

2018 ◽  
Vol 48 (6) ◽  
pp. 2528-2538 ◽  
Author(s):  
Shengjuan Wei ◽  
Mengmeng Zhang ◽  
Yueying Zheng ◽  
Peishi Yan
Keyword(s):  
Cell Model ◽  
Cell Counting ◽  
Brown Adipocyte ◽  
Mrna Levels ◽  
Mtdna Copy Number ◽  
Gpdh Activity ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Bovine Adipocytes

Background/Aims: Our study aims to characterize functions of ZBTB16 gene in the process of intramuscular fat (IMF) deposition and metabolism of bovine, thereby providing insights into mechanisms for the use of ZBTB16 in fat management. Methods: Primary preadipocytes derived from bovine IMF tissue were isolated and used as the in vitro cell model. An adenovirus Ad-ZBTB16 was transfected into bovine preadipocytes to overexpress the ZBTB16 gene. By using real-time quantitative PCR (RT-qPCR), western blotting, Oil Red-O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity assay, and cell counting kit-8 (CCK-8) test, adipogenic and proliferative signals in adipocytes were monitored to investigate effects of ZBTB16 on adipogenesis of bovine preadipocytes. Results: After transfection, mRNA and protein levels of ZBTB16 gene were significantly increased. Enhanced ZBTB16 significantly promoted preadipocyte differentiation, as evidenced by accelerated lipid accumulation, enhanced GPDH activity, consistently increased mRNA expressions of adipogenic key transcription factors PPARγ, C/EBPα, FABP4, and ADIPOQ, and markedly increased protein expressions of PPARγ and FABP4. No difference was observed concerning proliferation of preadipocytes after treatment with Ad-ZBTB16. Furthermore, relative mRNA levels of brown adipocyte selective genes (PRDM16, UCP1, Cidea, Cox8b, and PGC-1α) and beige adipocyte selective genes (CD137, TMEM26, and Tbx1) as well as UCP1 protein expression were significantly increased by Ad-ZBTB16. Meanwhile, Ad-ZBTB16 treatment remarkably induced mitochondrial biogenesis and increased relative mitochondrial DNA (mtDNA) copy number in bovine adipocytes. Conclusion: These results suggest that ZBTB16 overexpression can promote white adipogenesis and induce brown-like adipocyte formation for bovine white intramuscular preadipocytes.

scholarly journals The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway

2013 ◽  
Vol 24 (22) ◽  
pp. 3569-3576 ◽  
Author(s):  
Jarod Li ◽  
Marc S. Weinberg ◽  
Luiz Zerbini ◽  
Sharon Prince
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Preliminary Evidence ◽  
Transforming Growth Factor Β1 ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Breast Epithelial ◽  
Tgf Β1

The T-box transcription factor, TBX3, plays an important role in embryonic development, and haploinsufficiency of TBX3 causes ulnar–mammary syndrome. Overexpression of TBX3, on the other hand, is associated with several cancers, and preliminary evidence suggests that increased levels of TBX3 may inhibit cell proliferation but promote tumor migration and invasion. Although this suggests that deregulated levels of TBX3 are deleterious in development and promotes disease, very little is known about the signaling pathways that regulate TBX3 expression. Here we show that overexpressing TBX3 inhibits proliferative ability while promoting the migration of breast epithelial cells. We demonstrate that the transforming growth factor β1 (TGF-β1) pathway up-regulates TBX3 protein and mRNA levels and show a detailed transcriptional mechanism by which this occurs. Using in vitro and in vivo assays, we show that Smad3/4 and JunB bind and cooperatively regulate TBX3 promoter activity through a Smad-binding element at −67 base pairs. Further, we show that TBX3 plays a pivotal role in mediating the antiproliferative and promigratory role of TGF-β1 in breast epithelial and skin keratinocytes. This study identifies the TGF-β1 signaling pathway as a potentially important player in the regulation of TBX3 in development and cancer.

scholarly journals MiR-106b-5p regulates the migration and invasion of colorectal cancer cells by targeting FAT4

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Min Pan ◽  
Qiuqiu Chen ◽  
Yusong Lu ◽  
Feifei Wei ◽  
Chunqiao Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Scratch Test ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Messenger Rnas ◽  
Colorectal Cancer Cells

Abstract MicroRNA-106b-5p (miR-106b-5p) is involved in the development of many cancers including colorectal cancer (CRC), and FAT4 is correlated with regulation of growth and apoptosis of cancer cells. The present study aimed to investigate the relation between FAT4 and miR-106b-5p and the underlying mechanism of the two on the development of CRC. Quantitative real-time PCR (qRT-PCR) assay and Western blot (WB) analysis were performed to detect the expressions of messenger RNAs (mRNAs), microRNAs (miRNAs) and proteins. The viability of CRC cells was detected by cell counting kit-8 (CCK-8). Scratch test and transwell assay were performed to measure the migration and invasion of CRC cell. Tumor angiogenesis was simulated by in vitro angiogenesis experiment. Dual-luciferase reporter assay was performed to verify the targeting relation between miR-106b-5p and FAT4. The study found that the expression of FAT4 was down-regulated and that of miR-106b-5p was up-regulated in CRC tissues. Overexpression of FAT4 resulted in decreased proliferation, migration, invasion and angiogenesis of CRC cells, whereas silencing of FAT4 led to the opposite results. In rescue experiment, miR-106b-5p partially reversed the function of FAT4 in CRC cells, thus playing a carcinogenic role by targeting FAT4 in the CRC cells.

scholarly journals SWAP-70 promotes glioblastoma cellular migration and invasion by regulating the expression of CD44s

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Shi ◽  
Huize Liu ◽  
Yifeng Wang ◽  
Yulong Chong ◽  
Jie Wang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Expression ◽  
Malignant Tumors ◽  
Standard Form ◽  
Underlying Mechanism ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Nucleotide Exchange ◽  
Cell Migration And Invasion

Abstract Background Switch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors. However, the mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated. Methods This study used an online database to analyze the relationship between SWAP-70 expression and prognosis in GB patients. The in vitro wound healing assay and transwell invasion assay were used to determine the role of SWAP-70 in GB cell migration and invasion as well as the underlying mechanism. Results We found that patients with high SWAP-70 expression in the GB had a poor prognosis. Downregulation of SWAP-70 inhibited GB cell migration and invasion, whereas SWAP-70 overexpression had an opposite effect. Interestingly, SWAP-70 expression was positively correlated with the expression of the standard form of CD44 (CD44s) in GB tissues. Downregulation of SWAP-70 also reduced CD44s protein expression, whereas SWAP-70 overexpression enhanced CD44s protein expression. However, downregulation of SWAP-70 expression did not affect the mRNA expression of CD44s. Reversal experiments showed that overexpressing CD44s in cell lines with downregulated SWAP-70 partially abolished the inhibitory effects of downregulated SWAP-70 on GB cell migration and invasion. Conclusions These results suggest that SWAP-70 may promote GB cell migration and invasion by regulating the expression of CD44s. SWAP-70 may serve as a new biomarker and a potential therapeutic target for GB.

scholarly journals Oleanolic acid mediated the proliferation and invasion of U251 glioma cells and promoted their apoptosis through the IKK-β, MAPK3, and MAPK4 signaling pathway

2021 ◽  
Author(s):  
Jinxiang Huang ◽  
Shengnan Lin ◽  
Feng Zhu ◽  
Dengsheng Chen ◽  
Fang Huang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Western Blot Assay ◽  
Expression Levels ◽  
U251 Cells

Abstract ObjectTo investigate the effects of Oleanolic acid (OA) on proliferation, apoptosis, migration, and invasion of human glioma cell U251, as well as IKK-β and MAPK signaling pathways.MethodsThe binding of OA to IKK-β and MAPK signaling pathway essential proteins IKK-β, MAPK3, and MAPK4 was analyzed by molecular docking technique. U251 cells were treated with different concentrations of OA. The proliferation and apoptosis rates of U251 cells were detected by CCK-8 assay, MTT assay, cell cloning assay, and AnnexinⅤ FITC/PI double staining assay. Transwell chamber assay was used to detect migration and invasion of U251 cells. Finally, Western blotting was used to detect the protein expression levels of IKK-β, MAPK3, and MAPK4 in U251 cells treated with OA.ResultsThe results of molecular docking showed that OA could stably bind to IKK-β, MAPK3, and MAPK4 proteins. OA could not only effectively inhibit the proliferation and induce apoptosis of U251 cells (P < 0.05), but also significantly inhibit the invasion of U251 cells (P < 0.05). Western blot assay confirmed that OA could dramatically inhibit the protein expression levels of IKK-β, MAPK3, and MAPK4 in U251 cells (P < 0.05).ConclusionsOA may inhibit the proliferation, migration, and invasion of glioma U251 cells by binding key molecules of the IKK-β signaling pathway and essential target proteins of MAPK3 and MAPK4 in the MAPK signaling pathway.

scholarly journals Overexpression of FBXO17 Promotes the Proliferation, Migration and Invasion of Glioma Cells Through the Akt/GSK-3β/Snail Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972110073
Author(s):  
Ning Wang ◽  
Qian Song ◽  
Hai Yu ◽  
Gang Bao
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Vimentin Expression ◽  
Protein Levels ◽  
Cellular Behaviors ◽  
Gsk 3Β

FBXO17 is a newly studied F-box protein associated with high-grade glioma. However, its exact role in glioma remains unclear. In the present study, we aimed to investigate the role of FBXO17 in glioma both in vitro and in vivo and explore the underlying mechanism. Our results showed that FBXO17 mRNA and protein levels were upregulated in glioma cells including U87, U251, SHG44, and U-118-MG cells as compared to the HA1800 cells. Downregulation of FBXO17 significantly suppressed the cellular behaviors of glioma cells including cell proliferation, migration, and invasion. In addition, FBXO17 knockdown induced E-cadherin expression and inhibited N-cadherin and vimentin expression at mRNA and protein levels in glioma cells. In contrast, overexpression of FBXO17 promoted cell proliferation, migration, invasion and EMT process. Furthermore, FBXO17 regulated the Akt/GSK-3β/snail signaling pathway in glioma cells with significant changes in the expression levels of p-Akt, p-GSK-3β and snail. Additionally, inhibition of Akt by LY294002 reversed the effects of FBXO17 overexpression on cellular behaviors of glioma cells. Finally, in vivo mouse xenograft assay proved that downregulation of FBXO17 suppresses the tumorigenesis of glioma. In conclusion, these findings demonstrated that FBXO17 acted as a promotor of glioma development via modulating Akt/GSK-3β/snail signaling pathway.

Metformin exerts anti-tumor effects via Sonic hedgehog signaling pathway by targeting AMPK in HepG2 cells

2022 ◽  
Author(s):  
Ang Hu ◽  
Zeming Hu ◽  
Jianming Ye ◽  
Yuwen Liu ◽  
Zhonghong Lai ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Hepg2 Cells ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Shh Pathway ◽  
Mrna And Protein Expression ◽  
Proliferation And Metastasis

Metformin, a traditional first-line pharmacologic treatment for type 2 diabetes, has recently been shown to impart anti-cancer effects on hepatocellular carcinoma (HCC). However, the molecular mechanism of metformin on its antitumor activity is still not completely clear. The Sonic hedgehog (Shh) signaling pathway is closely associated with the initiation and progression of HCC. Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin on the Shh pathway. The HCC cellular was induced in HepG2 cells by recombinant human Shh (rhShh). The effects of metformin on proliferation and metastasis were evaluated by proliferation, wound healing and invasion assays in vitro. The mRNA and protein expression levels of proteins related to the Shh pathway were measured by western blotting, quantitative PCR and immunofluorescence staining. Metformin inhibited rhShh-induced proliferation and metastasis. Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1. Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK. Our findings demonstrate that metformin can suppress the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.

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