scholarly journals Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

2016 ◽  
Vol 38 (6) ◽  
pp. 2173-2182 ◽  
Author(s):  
Lu Wang ◽  
Lei Yang ◽  
Ying Lu ◽  
Yingzhun Chen ◽  
Tianhua Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Molecular Mechanisms ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Signaling Mechanism ◽  
Inhibition Of Proliferation

Background/Aims: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. Methods: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. Results: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. Conclusion: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.

Dehydroandrographolide Inhibits Osteosarcoma Cell Growth and Metastasis by Targeting SATB2-mediated EMT

2019 ◽  
Vol 19 (14) ◽  
pp. 1728-1736
Author(s):  
Xuefeng Liu ◽  
Yonggang Fan ◽  
Jing Xie ◽  
Li Zhang ◽  
Lihua Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wound Healing ◽  
Cell Growth ◽  
Brdu Incorporation ◽  
Migration And Invasion ◽  
Therapeutic Drug ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Inhibition Of Proliferation ◽  
Predominant Component

Background:The 12-hydroxy-14-dehydroandrographolide (DP) is a predominant component of the traditional herbal medicine Andrographis paniculata (Burm. f.) Nees (Acanthaceae). Recent studies have shown that DP exhibits potent anti-cancer effects against oral and colon cancer cells.Objective:This investigation examined the potential effects of DP against osteosarcoma cell.Methods:A cell analyzer was used to measure cell viability. The cell growth and proliferation were performed by Flow cytometry and BrdU incorporation assay. The cell migration and invasion were determined by wound healing and transwell assay. The expression of EMT related proteins was examined by Western blot analysis.Results:In this study, we found that DP treatment repressed osteosarcoma (OS) cell growth in a dose-dependent manner. DP treatment significantly inhibited OS cell proliferation by arresting the cell cycle at G2/M phase. In addition, DP treatment effectively inhibited the migration and invasion abilities of OS cells through wound healing and Transwell tests. Mechanistic studies revealed that DP treatment effectively rescued the epithelialmesenchymal transition (EMT), while forced expression of SATB2 in OS cells markedly reversed the pharmacological effect of DP on EMT.Conclusion:Our data demonstrated that DP repressed OS cell growth through inhibition of proliferation and cell cycle arrest; DP also inhibited metastatic capability of OS cells through a reversal of EMT by targeting SATB2. These findings demonstrate DP’s potential as a therapeutic drug for OS treatment.

scholarly journals β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Guoying Zhang ◽  
Cheng Xue ◽  
Yiming Zeng
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Model ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Akt Pathway ◽  
Loss Of Function ◽  
Airway Stenosis

Abstract Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

PGM1 Suppresses Colorectal Cancer Cell Migration And Invasion by Regulating PI3K/ AKT Pathway

2021 ◽  
Author(s):  
Zhewen Zheng ◽  
Xue Zhang ◽  
Jian Bai ◽  
Long Long ◽  
Di Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colony Formation ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Cycle Arrest ◽  
Cancer Pathogenesis

Abstract BackgroundPhosphoglucomutase 1(PGM1) is known for its involvement in cancer pathogenesis. However, its biological role in colorectal cancer (CRC) is unknown. Here, we studied the functions and mechanisms of PGM1 in CRC.Methods We verified PGM-1 as a DEG by a comprehensive strategy of the TCGA-COAD dataset mining and computational biology. Relative levels of PGM-1 in CRC tumors and adjoining peritumoral tissue were identified by qRT-PCR, WB, and IHC staining in a tissue microarray. PGM1 functions were analyzed using CCK8, EdU, colony formation, cell cycle, apoptosis, and Transwell migration and invasion assays. The influence of PGM1 was further investigated using tumor formation in vivo.ResultsPGM1 mRNA and protein were both reduced in CRC and the reduction was related to CRC pathology and overall survival. PGM1 knockdown stimulated both proliferation and colony formation, promoting cell cycle arrest and apoptosis while overexpression has opposite effects in CRC cells both in vivo and in vitro. Furthermore, we lined the actions of PGM1 to the PI3K/ AKT pathway. ConclusionWe verified that PGM1 suppresses CRC through the PI3K/ AKT pathway. These results suggest the potential for targeting PGM1 in CRC therapies.

scholarly journals MiR-4310 Induced by SP1 targets PTEN to Promote Glioma Progression

2020 ◽  
Author(s):  
Wu Zhiyong ◽  
Luo Jie ◽  
Huang Tengyue ◽  
Yi Renhui ◽  
Ding Shengfeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Boyden Chamber ◽  
Luciferase Reporter Gene ◽  
Mobility Shift ◽  
Glioma Progression

Abstract Background: miRNAs have been reported to be involved in multiple biological processes of gliomas. Here, we aimed to analyze miR-4310 and its correlation genes involved in the tumor progression of human glioma.Methods: miR-4310 expression levels were examined in glioma and non-tumor brain (NB) tissues. The molecular mechanisms of miR-4310 expression and its effects on cell proliferation, migration, and invasion were explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) , Transwell chamber, Boyden chamber, and western blot analyses, as well as in vivo tumorigenesis in nude mice. The relationships among miR-4310, SP1, and phosphatase and tensin homolog (PTEN) were explored by chromatin immunoprecipitation (ChIP), agarose gel electrophoresis, electrophoresis mobility shift (EMSA), and dual luciferase reporter gene assays. Results: miR-4310 expression was upregulated in glioma tissues compared to NB. Overexpressed miR-4310 promoted glioma cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo . Inhibition of miR-4310 was sufficient to reverse these results. Mechanistic analyses revealed that miR-4310 promoted glioma progression through the PI3K/AKT pathway by targeting PTEN. Additionally, SP1 induced the expression of miR-4310 by binding to its promoter region. Conclusion: miR-4310 promotes the progression of glioma by targeting PTEN and activating the PI3K/AKT pathway meanwhile the expression of miR-4310 is induced by SP1.

scholarly journals The Long Non-coding RNA TMPO-AS1  Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination

2020 ◽  
Author(s):  
Yeyu Zhang ◽  
Yuxing Zhu ◽  
Mengqing Xiao ◽  
Yaxin Cheng ◽  
Dong He ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
E2f Transcription Factor ◽  
Rna Immunoprecipitation ◽  
Regulatory Loop

Abstract BackgroundBladder cancer (BC) is the most common malignant tumor of the urinary system. Increasing evidence indicates long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis, development, and progression. However, the role of TMPO antisense RNA 1 (TMPO-AS1) is still need to be explored in BC.MethodsThe lncRNA TMPO-AS1 expression was evaluated by bioinformatics analysis and further validated by qRT-PCR. Loss- and gain-of- function assays were performed to determine the biological functions of TMPO-AS1 in BC proliferation, migration, and invasion. Chromatin immunoprecipitation, luciferase reporter assays, western blotting, RNA pull-down, RNA immunoprecipitation assays, and fluorescence in situ hybridization were conducted to explore the molecular mechanisms of TMPO-AS1/E2F transcription factor 1 (E2F1) loop. ResultsTMPO-AS1 is upregulated in bladder cancer and is associated with BC patients’ poor prognoses. Functional experiments demonstrated that TMPO-AS1 promotes bladder cancer cell proliferation, migration, invasion, and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for the TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization, thereby promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner.ConclusionsOur study is the first to uncover a novel positive regulatory loop of TMPO-AS1/E2F1 important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.

Anlotinib Inhibits Cell Proliferation, Migration and Invasion via Suppression of c-met Pathway and Activation of ERK1/2 Pathway in H446 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiali Tang ◽  
Ying Zheng ◽  
Demin Jiao ◽  
Jun Chen ◽  
Xibang Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
M Cell ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
And Migration

Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.

Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion of MDA-MB-231 Triple-Negative Breast Cancer Cell via Induction of Autophagy

2020 ◽  
Vol 19 (16) ◽  
pp. 1983-1990 ◽  
Author(s):  
Hui-Yuan Lu ◽  
Jian-Sheng Zhu ◽  
Zhan Zhang ◽  
Wei-Jian Shen ◽  
Shan Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Viability ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cell Migration And Invasion

Background: Breast Cancer (BC) is the leading cause of cancer-related deaths among women. As such, novel chemotherapeutic agents are urgently needed, especially for Triple-Negative Breast Cancer (TNBC). Hydroxytyrosol (HT) and Oleuropein (OL) are rich in olive oil, which is associated with a low occurrence of BC. However, the effects and mechanisms of action of HT and OL in BC cells are still unclear. This study aimed to explore the molecular mechanisms underlying the antitumor effect of HT and OL in TNBC. Methods: TNBC MDA-MB-231 cells were treated with HT and OL in combination with Hepatocyte Growth Factor (HGF), rapamycin (Rapa, an inducer of autophagy) or 3-methyladenine (3-MA, an inhibitor of autophagy). Cell viability, migration, invasion, and autophagy signaling were analyzed by scratch assays, transwell migration assays, and Western blot analysis. Results: Treatment with HT or OL reduced MDA-MB-231 cell viability in a dose-dependent manner. MDAMB- 231 cells were more sensitive to HT treatment than OL treatment. Rapa treatment could significantly block HGF-induced MDA-MB-231 cell migration and invasion, suggesting that inhibition of autophagy could promote migration and invasion. Moreover, HT or OL treatment significantly suppressed HGF or 3-MA induced cell migration and invasion by reversing LC3-II/LC3-I and Beclin-1 downregulation and reversing p62 upregulation. Conclusion: These data indicated that HT and OL may inhibit migration and invasion of TNBC cells by activating autophagy. These findings provide potential therapeutic strategies that target autophagy to limit the pathogenesis and progression of BC.

scholarly journals Hippo signaling is intrinsically regulated during cell cycle progression by APC/CCdh1

2019 ◽  
Vol 116 (19) ◽  
pp. 9423-9432 ◽  
Author(s):  
Wantae Kim ◽  
Yong Suk Cho ◽  
Xiaohui Wang ◽  
Ogyi Park ◽  
Xueyan Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Mitotic Cell ◽  
Hippo Signaling ◽  
Dependent Manner ◽  
Large Tumor ◽  
Cycle Progression ◽  
Signaling Regulation

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/CCdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

scholarly journals Apigenin Inhibits the Growth of Hepatocellular Carcinoma Cells by Affecting the Expression of microRNA Transcriptome

2021 ◽  
Vol 11 ◽  
Author(s):  
Shou-Mei Wang ◽  
Pei-Wei Yang ◽  
Xiao-Jun Feng ◽  
Yi-Wei Zhu ◽  
Feng-Jun Qiu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Dependent Manner ◽  
Regulatory Pathways ◽  
The Core ◽  
Huh7 Cells

BackgroundApigenin, as a natural flavonoid, has low intrinsic toxicity and has potential pharmacological effects against hepatocellular carcinoma (HCC). However, the molecular mechanisms involving microRNAs (miRNAs) and their target genes regulated by apigenin in the treatment of HCC have not been addressed.ObjectiveIn this study, the molecular mechanisms of apigenin involved in the prevention and treatment of HCC were explored in vivo and in vitro using miRNA transcriptomic sequencing to determine the basis for the clinical applications of apigenin in the treatment of HCC.MethodsThe effects of apigenin on the proliferation, cell cycle progression, apoptosis, and invasion of human hepatoma cell line Huh7 and Hep3B were studied in vitro, and the effects on the tumorigenicity of Huh7 cells were assessed in vivo. Then, a differential expression analysis of miRNAs regulated by apigenin in Huh7 cells was performed using next-generation RNA sequencing and further validated by qRT-PCR. The potential genes targeted by the differentially expressed miRNAs were identified using a curated miRTarBase miRNA database and their molecular functions were predicted using Gene Ontology and KEGG signaling pathway analysis.ResultsCompared with the control treatment group, apigenin significantly inhibited Huh7 cell proliferation, cell cycle, colony formation, and cell invasion in a concentration-dependent manner. Moreover, apigenin reduced tumor growth, promoted tumor cell necrosis, reduced the expression of Ki67, and increased the expression of Bax and Bcl-2 in the xenograft tumors of Huh7 cells. Bioinformatics analysis of the miRNA transcriptome showed that hsa-miR-24, hsa-miR-6769b-3p, hsa-miR-6836-3p, hsa-miR-199a-3p, hsa-miR-663a, hsa-miR-4739, hsa-miR-6892-3p, hsa-miR-7107-5p, hsa-miR-1273g-3p, hsa-miR-1343, and hsa-miR-6089 were the most significantly up-regulated miRNAs, and their key gene targets were MAPK1, PIK3CD, HRAS, CCND1, CDKN1A, E2F2, etc. The core regulatory pathways of the up-regulated miRNAs were associated with the hepatocellular carcinoma pathway. The down-regulated miRNAs were hsa-miR-181a-5p and hsa-miR-148a-3p, and the key target genes were MAPK1, HRAS, STAT3, FOS, BCL2, SMAD2, PPP3CA, IFNG, MET, and VAV2, with the core regulatory pathways identified as proteoglycans in cancer pathway.ConclusionApigenin can inhibit the growth of HCC cells, which may be mediated by up-regulation or down-regulation of miRNA molecules and their related target genes.

scholarly journals MiR-4310 induced by SP1 targets PTEN to promote glioma progression

2020 ◽  
Author(s):  
Wu Zhiyong ◽  
Luo Jie ◽  
Huang Tengyue ◽  
Yi Renhui ◽  
Ding Shengfeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Boyden Chamber ◽  
Luciferase Reporter Gene ◽  
Mobility Shift ◽  
Glioma Progression

Abstract Background: miRNAs have been reported to be involved in multiple biological processes of gliomas. Here, we aimed to analyze miR-4310 and its correlation genes involved in the tumor progression of human glioma. Methods: miR-4310 expression levels were examined in glioma and non-tumor brain (NB) tissues. The molecular mechanisms of miR-4310 expression and its effects on cell proliferation, migration, and invasion were explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) , Transwell chamber, Boyden chamber, and western blot analyses, as well as in vivo tumorigenesis in nude mice. The relationships among miR-4310, SP1, and phosphatase and tensin homolog (PTEN) were explored by chromatin immunoprecipitation (ChIP), agarose gel electrophoresis, electrophoresis mobility shift (EMSA), and dual luciferase reporter gene assays. Results: miR-4310 expression was upregulated in glioma tissues compared to NB. Overexpressed miR-4310 promoted glioma cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo . Inhibition of miR-4310 was sufficient to reverse these results. Mechanistic analyses revealed that miR-4310 promoted glioma progression through the PI3K/AKT pathway by targeting PTEN. Additionally, SP1 induced the expression of miR-4310 by binding to its promoter region. Conclusion: miR-4310 promotes the progression of glioma by targeting PTEN and activating the PI3K/AKT pathway meanwhile the expression of miR-4310 is induced by SP1.

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