Latent Membrane Protein 1 Antibody Inhibited Cell Stemness Growth of Nasopharyngeal Carcinoma by Regulating PI3K/AKT Signaling Pathway

2020 ◽  
Vol 10 (6) ◽  
pp. 768-775
Author(s):  
Dawei Zhang ◽  
Lin Xiong ◽  
Liang Li ◽  
Yuan Chen ◽  
Xiaojun Tang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Latent Membrane Protein 1 ◽  
The Novel ◽  
Akt Signaling Pathway ◽  
Akt Phosphorylation ◽  
Sphere Formation

Objective: The aim of the study was to investigate the effects of LMP1-Fab antibody on Nasopharyngeal carcinoma (NPC) cancer stem cells (CSCs). Methods/Results: LMP1 was identified to play an important role in maintaining the stemness characteristics of NPC by sphere formation, as is evidenced by CCK-8 and colony formation assays. Furthermore, CCK8 and TUNEL assays indicated that LMP1-Fab antibody could accelerate cell apoptosis while inhibiting cell proliferation in nasopharyngeal carcinoma stem cell. Notably, LMP1-Fab antibody inhibited NPC xenograft cancer growth in the nude mice. At the molecular level, LMP1-Fab antibody inhibited the phosphorylation of PI3K/AKT signaling pathway both in vitro and in vivo. More importantly, these effects were blocked by PI3K/AKT phosphorylation inhibitor LY294002. Conclusion: These results suggested that the novel antibody-targeting LMP1 is likely to be a promising strategy for the treatment of NPC.

scholarly journals YBX3 Mediates the Metastasis of Nasopharyngeal Carcinoma via PI3K/AKT Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoqin Fan ◽  
Xina Xie ◽  
Ming Yang ◽  
Yujie Wang ◽  
Hanwei Wu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
Akt Signaling ◽  
Ras Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

The metastasis of nasopharyngeal carcinoma (NPC) is a complex process associated with oncogenic dysfunction, the deciphering of which remains a challenge and requires more in-depth studies. Y-box protein 3 (YBX3) is a DNA/RNA binding protein associated with gene transcription, DNA repair, and the progression of various diseases. However, whether and how YBX3 affects the metastasis of NPC remains unknown. Thus, in this study, we aimed to investigate the role of YBX3 in the metastasis of NPC and determine its underlying mechanism. Interestingly, it was found that the expression of YBX3, which was associated with NPC metastasis, was upregulated in the clinical NPC tissues and cell lines. Moreover, we found that knockdown of YBX3 expression by lentivirus shRNA significantly suppressed NPC cells migration in vitro and metastasis in vivo. Mechanistically, RNA sequencing results suggested that the genes regulated by YBX3 were significantly enriched in cell adhesion molecules, cAMP signaling pathway, calcium signaling pathway, focal adhesion, PI3K/AKT signaling pathway, Ras signaling pathway, Rap1 signaling pathway, NF-κB signaling pathway, and Chemokine signaling pathway. Of these, PI3K/AKT signaling pathway contained the most genes. Accordingly, YBX3 knockdown decreased the activation of PI3K/AKT signaling pathway, thereby inhibit epithelial-to-mesenchymal transition (EMT) and MMP1. These results have demonstrated that YBX3 are involved in the metastasis of NPC through regulating PI3K/AKT signaling pathway, and serve as a potential therapeutic target for patients with NPC.

A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice

2018 ◽  
Vol 132 (6) ◽  
pp. 685-699 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Xin Zhang ◽  
Yu-Pei Yuan ◽  
Ya-Ge Jin ◽  
Ning Li ◽  
...  
Keyword(s):  
T Cell ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Akt Signaling Pathway

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro. In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro. Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro. More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

Cyanidin inhibits EMT induced by oxaliplatinviatargeting the PDK1–PI3K/Akt signaling pathway

2019 ◽  
Vol 10 (2) ◽  
pp. 592-601 ◽  
Author(s):  
Xiang Li ◽  
Ze-sheng Zhang ◽  
Xiao-han Zhang ◽  
Sheng-nan Yang ◽  
Dong Liu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Anthocyanins have been shown to exhibit antitumor activity in several cancersin vitroandin vivo.

scholarly journals Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Changsheng Nai ◽  
Haochen Xuan ◽  
Yingying Zhang ◽  
Mengxiao Shen ◽  
Tongda Xu ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Signaling Pathway ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Myocardial Infarct Size ◽  
Akt Signaling Pathway ◽  
Cardioprotective Effects

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

scholarly journals Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway

2018 ◽  
Vol 36 (5) ◽  
pp. 743-754 ◽  
Author(s):  
Piming Zhao ◽  
Ana E. Aguilar ◽  
Joanna Y. Lee ◽  
Lucy A. Paul ◽  
Jung H. Suh ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Therapeutic Efficacy ◽  
Akt Signaling ◽  
Akt Signaling Pathway

PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway

2019 ◽  
Vol 120 (10) ◽  
pp. 17887-17897 ◽  
Author(s):  
Yongchao Du ◽  
Peihua Liu ◽  
Zhi Chen ◽  
Yao He ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Akt Signaling ◽  
Akt Signaling Pathway

scholarly journals MiR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth

2021 ◽  
Author(s):  
Jingyan Li ◽  
Zhanlei Zhang ◽  
Jieting Hu ◽  
Xiaoting Wan ◽  
Wei Huang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Gene Expression Omnibus ◽  
Akt Signaling ◽  
Akt Phosphorylation ◽  
Apoptotic Death ◽  
Phosphoinositide 3 Kinase

AbstractOne of the most prevalent forms of endocrine malignancies is thyroid cancer. Herein, we explored the mechanisms whereby miR-1246 is involved in thyroid cancer. Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1) was identified as a potential miR-1246 target, with the online Gene Expression Omnibus (GEO) database. The binding between miR-1246 and PIK3AP1 and the dynamic role of these two molecules in downstream PI3K/AKT signaling were evaluated. Analysis of GEO data demonstrated significant miR-1246 downregulation in thyroid cancer, and we confirmed that overexpression of miR-1246 can inhibit migratory, invasive, and proliferative activity in vitro and tumor growth in vivo. Subsequent studies indicated that miR-1246 overexpression decreased the protein level of PIK3AP1 and the phosphorylation of PI3K and AKT, which were reversed by PIK3AP1 overexpression. At the same time, overexpression of PIK3AP1 also reversed the miR-1246 mimics-induced inhibition proliferative, migratory, and invasive activity, while promoting increases in apoptotic death, confirming that miR-1246 function was negatively correlated with that of PIK3AP1. Subsequently, we found that the miR-1246 mimics-induced inhibition of PI3K/AKT phosphorylation was reversed by the PI3K/AKT activator IGF-1. miR-1246 mimics inhibited proliferative, migratory, and invasive activity while promoting increases in apoptotic death, which were reversed by IGF-1. Furthermore, miR-1246 agomir can inhibit tumor growth in vivo. We confirmed that miR-1246 affects the signaling pathway of PI3K/AKT via targeting PIK3AP1 and inhibits the development of thyroid cancer. Thus, miR-1246 is a new therapeutic target for thyroid cancer.

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