scholarly journals Interfering with pak4 Protein Expression Affects Osteosarcoma Cell Proliferation and Migration

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yuxin Fu ◽  
Lun Fang ◽  
Qipu Yin ◽  
Qi Wu ◽  
Wei Sui ◽  
...  
Keyword(s):  
Protein Expression ◽  
Osteosarcoma Cell ◽  
Mrna Levels ◽  
Osteosarcoma Cells ◽  
Migration Ability ◽  
M Phase ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Proliferation And Migration

Purpose. A number of studies have discovered various roles of PAK4 in human tumors, including osteosarcoma. However, the exact role of PAK4 in osteosarcoma and its mechanism have yet to be determined. Therefore, this study focused on interrogating the PAK4 effect on the proliferation and migration ability of osteosarcoma and its underlying mechanisms. Materials and Methods. Western blot and QRT-PCR were utilized to quantify the PAK4 relative protein and mRNA levels. To measure cellular viability and mobility, the MTT and wound-healing assays were preferred. Results. With the adenovirus-mediated overexpression of PAK4, the proliferation and migration of U2-OS and MG-63 osteosarcoma cells were stimulated. Furthermore, a liposome-mediated knockout of PAK4 will inhibit osteosarcoma cells from proliferating. In terms of mechanism, we observed the positive correlation of PAK4 expression with expression of P21, CyclinD1, CyclinE1, CDK2, and CDK6, which drives G0/G1 to the G2/M phase transition. PAK4 can also activate Erk expression in OS cells and induce EMT. Conclusion. Interfering with PAK4 protein expression has been shown to affect osteosarcoma proliferation and migration.

Using Bioinformatics Analysis to Detect the Effect of Zoledronic Acid on the Biological Behavior of Osteosarcoma Cells

2019 ◽  
Vol 9 (8) ◽  
pp. 1568-1574
Author(s):  
Sheng Li ◽  
Jianjun Li
Keyword(s):  
Cell Proliferation ◽  
Zoledronic Acid ◽  
Side Effects ◽  
Bioinformatics Analysis ◽  
Biological Behavior ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Migration Ability ◽  
And Migration ◽  
Proliferation And Migration

Objective: Osteosarcoma is a malignant bone tumor commonly seen in adolescents. Drug treatment for osteosarcoma is often accompanied by systemic toxicity and side effects, while zoledronic acid has few side effects but has anti-tumor effects. Methods: The bioinformatics analysis and scratch test were used to detect changes in cell proliferation, migration, and apoptosis in two osteosarcoma cell lines 24, 48, and 72 hours after adding zoledronic acid (0, 25, 50, 100, and 200 μM). Flow cytometry and transmission electron microscopy were used to observe the changes in cell apoptosis in the control and experimental groups after a 50% inhibitory dose of zoledronic acid was given. Results: The inhibition of cell proliferation and migration ability, as well as apoptosis increased with the increase in zoledronic acid exposure time and concentration. The 50% inhibitory rate occurred 48 hours after treatment with 100 M zoledronic acid. Conclusion: Zoledronic acid inhibited proliferation and migration and promoted apoptosis of osteosarcoma cells in vitro.

Posttranscriptional inhibition of γ-adducin promotes the proliferation and migration of osteosarcoma cells

2021 ◽  
pp. 030089162110506
Author(s):  
Zhigang Suo ◽  
Xiucai Ma ◽  
Yueping Ding ◽  
Yu Zhou ◽  
Xiangguo Duan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Annexin V ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Luciferase Reporter Gene ◽  
And Migration ◽  
Proliferation And Migration

Objective: The expression of cytoskeleton-related protein γ-adducin (ADD3) was abnormally reduced in some tumors. Functional experiments demonstrated that it could inhibit the malignant progression of lung cancer and glioma, whereas the involvement of ADD3 in osteosarcoma was not clear. This study aimed to investigate the role of ADD3 in osteosarcoma and its upstream regulatory mechanisms. Methods: ADD3 was knocked down by siRNA transfection and the expression level of ADD3 was determined using quantitative real-time PCR assay and Western blot. CCK-8 assay and colony formation were performed to detect the capacity of cell proliferation. Transwell assay and PI and Annexin V-FITC staining were used to determine cell migration and apoptosis, respectively. Luciferase reporter experiment was performed to investigate the interaction between ADD3 and miR-23b-3p. Results: Based on gene silencing assays, we showed that knockdown of ADD3 suppressed apoptosis and promoted the proliferation and migration of osteosarcoma cells, revealing inhibitory effects of ADD3 in osteosarcoma. Luciferase reporter gene assays confirmed that miR-23b-3p could bind to the 3'-UTR of ADD3. Upregulation of miR-23b-3p not only inhibited the expression of ADD3, but also released the tumor suppressive role of ADD3 on the proliferation and migration of osteosarcoma cells. Conclusions: Our study found that ADD3 functioned as a tumor suppressor gene during osteosarcoma development. The abnormal upregulation of miR-23b-3p targeted the expression of ADD3 and resulted in accelerated osteosarcoma cell proliferation and migration. Thus, the miR-23b-3p/ADD3 axis contributes to the development of osteosarcoma and ADD3 is a key driver of malignancy.

scholarly journals HDAC6 Inhibitor WT161 Performs Antitumor Effect on Ostersarcoma and Synergistically Interacts with 5-FU

2020 ◽  
Author(s):  
Jun Sun ◽  
Xiaofeng Tang ◽  
Feifei Zhang ◽  
Cheng Ju ◽  
Renfeng Liu ◽  
...  
Keyword(s):  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Proliferative Effect ◽  
Xenograft Models ◽  
Hdac6 Inhibitor ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract Background: WT161 as a new selective HDAC6 inhibitor has been shown to play anti-tumor effects on multiple myeloma and breast cancer. However, the role of WT161 in osteosarcoma remains unclear. The aim of this study is to explore the role of WT161 in osteosarcoma and its underlying mechanisms.Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were esatablished to evaluate the anti-proliferative effect of WT161 in vivo.Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein expression level of PTEN and decreased the phosphorylation level of AKT. Notably, WT161 shows synergistically inhibitory effects on osteosarcoma cell combined with 5-FU. Animal experiment results show WT161 inhibits the growth of osteosarcoma tumor and further illustrates that WT161 and 5-FU have a synergistic efficiency in osteosarcoma.Conclusions: These results indicate that WT161 inhibiting the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

scholarly journals Role of Phosphodiesterase2A in Proliferation and Migration of Human Osteosarcoma Cells

2019 ◽  
Vol 39 (11) ◽  
pp. 6057-6062
Author(s):  
TAKU MURATA ◽  
KASUMI SHIMIZU ◽  
KAZUTO KUROHARA ◽  
AKIRA TOMEOKU ◽  
GAKU KOIZUMI ◽  
...  
Keyword(s):  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Cao ◽  
Li Xu ◽  
Xiaohong Yang ◽  
Yuan Dong ◽  
Hongbin Luo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Cell Counting ◽  
Migration Ability ◽  
Cell Growth And Migration ◽  
Cell Based Therapy ◽  
And Migration ◽  
Proliferation And Migration

Background. Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden. Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes. The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds. Methods. Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor). A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and β-catenin knockdown cell line. Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration. The activation of TERT, β-catenin, and c-Myc was determined using real-time qPCR and western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/β-catenin signals. Results. CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, β-catenin, c-Myc. These effects of CAG were most pronounced at a dose of 0.3 μM. Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and β-catenin-silenced cells. In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/β-catenin signaling. Conclusion. Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/β-catenin signaling.

scholarly journals Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone

2018 ◽  
Vol 51 (5) ◽  
pp. 2472-2483 ◽  
Author(s):  
Chenglong Zhao ◽  
Dongsheng Wang ◽  
Liang Tang ◽  
Zhichao Zhang ◽  
Song Li ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Mononuclear Cells ◽  
Bone Destruction ◽  
Cell Tumor ◽  
Migration Ability ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. Methods: We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. Results: CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. Conclusion: Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.

scholarly journals miR-194 Suppresses Proliferation and Migration and Promotes Apoptosis of Osteosarcoma Cells by Targeting CDH2

2018 ◽  
Vol 45 (5) ◽  
pp. 1966-1974 ◽  
Author(s):  
Jinglei Miao ◽  
Weiguo Wang ◽  
Song Wu ◽  
Xiaofang Zang ◽  
Yuezhan Li ◽  
...  
Keyword(s):  
Tumour Suppressor ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Migration Assay ◽  
Tumour Suppression ◽  
Normal Bone ◽  
Proliferation Ability ◽  
And Migration ◽  
Normal Bone Tissue ◽  
Proliferation And Migration

Background/Aims: Studies have shown that miR-194 functions as a tumour suppressor and is associated with tumour growth and metastasis. This study intends to uncover the mechanism of tumour suppression by miR-194. The expression of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. Methods: The proliferation ability was examined by MTT assay. Migration and apoptosis of cells were monitored by migration assay and flow cytometry, respectively. The regulation of miR-194 on CDH2 was determined by luciferase assays and western blot assays. Results: The results showed that miR-194 was significantly reduced in osteosarcoma compared with that in normal bone tissue. Overexpression of miR-194 significantly attenuated the proliferation and migration and induced the apoptosis of osteosarcoma cells. Furthermore, we demonstrated that miR-194 has inhibited the malignant behaviour of osteosarcoma by downregulating CDH2 expression. Conclusions: These findings suggested that miR-194 may act as a tumour suppressor in osteosarcoma. miR-194/CDH2 may be a novel therapeutic target in the treatment of osteosarcoma.

scholarly journals Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402093713 ◽  
Author(s):  
Andrew J. McNair ◽  
Kathryn S. Wilson ◽  
Patricia E. Martin ◽  
David J. Welsh ◽  
Yvonne Dempsie
Keyword(s):  
Pulmonary Artery ◽  
Protein Expression ◽  
Connexin 43 ◽  
Pulmonary Vasculature ◽  
Hypoxic Exposure ◽  
In Vivo Models ◽  
Cx43 Protein ◽  
And Migration ◽  
Proliferation And Migration

Pulmonary hypertension (PH) is a disease associated with vasoconstriction and remodelling of the pulmonary vasculature. Pulmonary artery fibroblasts (PAFs) play an important role in hypoxic-induced remodelling. Connexin 43 (Cx43) is involved in cellular communication and regulation of the pulmonary vasculature. Using both in vitro and in vivo models of PH, the aims of this study were to (i) investigate the role of Cx43 in hypoxic-induced proliferation and migration of rat PAFs (rPAFs) and rat pulmonary artery smooth muscle cells (rPASMCs) and (ii) determine whether Cx43 expression is dysregulated in the rat sugen5416/hypoxic model of PH. The role of Cx43 in hypoxic-induced proliferation and migration was investigated using Gap27 (a pharmacological inhibitor of Cx43) or genetic knockdown of Cx43 using siRNA. Cx43 protein expression was increased by hypoxia in rPAFs but not rPASMCs. Hypoxic exposure, in the presence of serum, resulted in an increase in proliferation of rPAFs but not rPASMCs. Hypoxic exposure caused migration of rPAFs but not rPASMCs. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were increased by hypoxia in rPAFs. The effects of hypoxia on proliferation, migration and MAPK phosphorylation in rPAFs were attenuated in the presence of Gap27 or Cx43 siRNA. Cx43 protein expression was increased in sugen5416/hypoxic rat lung; this increased expression was not observed in sugen5416/hypoxic rats treated with the MAPK pathway inhibitor GS-444217. In conclusion, Cx43 is involved in the proliferation and migration of rPAFs in response to hypoxia via the MAPK signalling pathway.

Sign in / Sign up

Export Citation Format

Share Document