Combinatorial therapy with adenoviral-mediated PTEN and a PI3K inhibitor suppresses malignant glioma cell growth in vitro and in vivo by regulating the PI3K/AKT signaling pathway

Abstract Background: Gallbladder cancer (GBC) is the most common malignant tumour of the bile duct with a poor prognosis. The estrogen-related receptor alpha (ERRα) is a nuclear receptor that has been associated with metabolic processes and cancer progression. Increased ERRα has been shown in endocrine-related cancer and non-endocrine-related cancer. Nevertheless, its role in GBC remains unknown. Methods: ERRα expression was analyzed by immunohistochemistry in 59 GBC samples. Its association with clinicopathologic characteristics was evaluated. The effect of ERRα on GBC cell proliferation and invasion was evaluated by loss- or gain-of-function assays in vitro and in vivo. The influence of ERRα on EMT biomarkers, Nectin-4 and PI3K/AKT signaling pathway was detected by western blotting. Inhibition of Nectin-4 was conducted to explore the potential mechanism of ERRα in GBC. Results: Our study reveals increased ERRα expression in GBC tissues vs. non-tumour adjacent tissues. ERRα expression is significantly positively correlated with high TNM stage, high invasion depth and lymph node metastasis, while negatively associated with prognosis. Targeted depletion of ERRα by lentivirus-mediated shRNA decreased cell proliferation in vitro and in vivo. ERRα promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of EMT relevant genes. Ectopic expression of ERRα promoted GBC cell growth and invasion in vitro, while inhibiton of Nectin-4 attenuated cell growth and invasion induced by ERRα. Moreover, ERRα overexpression activated the PI3K/AKT signaling pathway while this effect can be blocked by Nectin-4 depletion. Nectin-4 was involved in the oncogenic function of ERRα to activate PI3K/AKT signaling pathway in GBC. Conclusions: ERRα promotes GBC progression via activating PI3K/AKT signaling pathway mediated by Nectin-4. ERRα may be a potential prognostic factor and molecular therapeutic target for GBC.

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Squamosamide derivative FLZ protected dopaminergic neuron by activating Akt signaling pathway in 6-OHDA-induced in vivo and in vitro Parkinson's disease models

Brain Research ◽

10.1016/j.brainres.2013.12.026 ◽

2014 ◽

Vol 1547 ◽

pp. 49-57 ◽

Cited By ~ 17

Author(s):

Xiu-Qi Bao ◽

Xiang-Chen Kong ◽

Li-Bing Kong ◽

Liang-Yu Wu ◽

Hua Sun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Signaling Pathway ◽

Dopaminergic Neuron ◽

Akt Signaling ◽

Disease Models ◽

Akt Signaling Pathway

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

Clinical Science ◽

10.1042/cs20180160 ◽

2018 ◽

Vol 132 (6) ◽

pp. 685-699 ◽

Cited By ~ 20

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.

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

Food & Function ◽

10.1039/c8fo01611a ◽

2019 ◽

Vol 10 (2) ◽

pp. 592-601 ◽

Cited By ~ 6

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.

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In vitro and in vivo Induction of p53-Dependent Apoptosis by Extract of Euryale ferox Salisb in A549 Human Caucasian Lung Carcinoma Cancer Cells Is Mediated Through Akt Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2019.00406 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Gun-He Nam ◽

Kyung-Jo Jo ◽

Ye-Seul Park ◽

Hye Won Kawk ◽

Sang-Yong Kim ◽

...

Keyword(s):

Cancer Cells ◽

Signaling Pathway ◽

Lung Carcinoma ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Euryale Ferox ◽

In Vivo Induction

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/365854 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 9

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.

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