scholarly journals Diallyl disulfide inhibits the metastasis of type Ⅱ esophageal‑gastric junction adenocarcinoma cells via NF-κB and PI3K/AKT signaling pathways in vitro

2017 ◽  
Author(s):  
Xiaoran Yin ◽  
Cheng Feng ◽  
Lili Han ◽  
Yinan Ma ◽  
Yang Jiao ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Akt Signaling ◽  
Diallyl Disulfide ◽  
Adenocarcinoma Cells

scholarly journals Tanshinone IIA Inhibits Osteosarcoma Growth through a Src Kinase-Dependent Mechanism

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Chao Hu ◽  
Xiaobin Zhu ◽  
Taogen Zhang ◽  
Zhouming Deng ◽  
Yuanlong Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Src Kinase ◽  
Akt Signaling ◽  
Cellular Level ◽  
Tanshinone Iia

Introduction. Osteosarcoma is a malignant tumor associated with high mortality rates due to the toxic side effects of current therapeutic methods. Tanshinone IIA can inhibit cell proliferation and promote apoptosis in vitro, but the exact mechanism is still unknown. The aims of this study are to explore the antiosteosarcoma effect of tanshinone IIA via Src kinase and demonstrate the mechanism of this effect. Materials and Methods. Osteosarcoma MG-63 and U2-OS cell lines were stable transfections with Src-shRNA. Then, the antiosteosarcoma effect of tanshinone IIA was tested in vitro. The protein expression levels of Src, p-Src, p-ERK1/2, and p-AKt were detected by Western blot and RT-PCR. CCK-8 assay and BrdU immunofluorescence assay were used to detect cell proliferation. Transwell assay, cell scratch assay, and flow cytometry were used to detect cell invasion, migration, and cell cycle. Tumor-bearing nude mice with osteosarcoma were constructed. The effect of tanshinone IIA was detected by tumor HE staining, tumor inhibition rate, incidence of lung metastasis, and X-ray. Results. The oncogene role of Src kinase in osteosarcoma is reflected in promoting cell proliferation, invasion, and migration and in inhibiting apoptosis. However, Src has different effects on cell proliferation, apoptosis, and cell cycle regulation among cell lines. At a cellular level, the antiosteosarcoma effect of tanshinone IIA is mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. At the animal level, tanshinone IIA played a role in resisting osteosarcoma formation by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. Conclusion. Tanshinone IIA plays an antiosteosarcoma role in vitro and in vivo and inhibits the progression of osteosarcoma mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.

Alpha mangostin Inhibits Hepatic Stellate Cells Activation Through TGF-β/Smad and Akt Signaling Pathways: An in vitro Study in LX2

Drug Research ◽  
2017 ◽  
Vol 68 (03) ◽  
pp. 153-158 ◽  
Author(s):  
Rahmaniah Rahmaniah ◽  
Yuyuntia Yuyuntia ◽  
Vivian Soetikno ◽  
Wawaimuli Arozal ◽  
Radiana Antarianto ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Akt Signaling ◽  
Dependent Manner ◽  
Trypan Blue Exclusion ◽  
Ki 67 ◽  
Trypan Blue Exclusion Method ◽  
Dose Dependent

Abstract Background Alpha mangostin has been reported to have activity for the treatment of liver fibrosis in the rats. However, the mechanisms of action are poorly understood. This study was aimed to investigate the effect of alpha mangostin on hepatic stellate cells (HSC) activation and proliferation through TGF-β/Smad and Akt signaling pathways. Methods Immortalized HSC, LX2 cells, were incubated with TGF-β with or without alpha mangostin (5 or 10 μM). Sorafenib 10 µM was used as positive control. LX2 viability was counted using trypan blue exclusion method. The effect of alpha mangostin on TGF-β concentrations, and the expressions of proliferation and fibrogenic markers were evaluated. Results Alpha mangostin treatment resulted in a reduced proliferation of HSC, decreased Ki-67 and p-Akt expressions. These findings were followed with decreased concentrations of TGF-β in the medium of cells treated with alpha mangostin, decreased expressions of COL1A1, TIMP1, PAI1, α-SMA, and p-Smad3 as fibrogenic markers. These effects were shown to be dose-dependent. Conclusions Alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF-β/Smad and Akt signaling pathways in dose dependent manner.

scholarly journals Metformin alleviates the calcification of aortic valve interstitial cells through activating the PI3K/AKT pathway in an AMPK dependent way

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Qiao En ◽  
Huang Zeping ◽  
Wang Yuetang ◽  
Wang Xu ◽  
Wang Wei
Keyword(s):  
Aortic Valve ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Interstitial Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Aortic Valves ◽  
Valve Interstitial Cells ◽  
Pathological Mechanism

Abstract Background Calcific aortic valve disease (CAVD) is the most prevalent valvular disease worldwide. However, no effective treatment could delay or prevent the progression of the disease due to the poor understanding of its pathological mechanism. Many studies showed that metformin exerted beneficial effects on multiple cardiovascular diseases by mediating multiple proteins such as AMPK, NF-κB, and AKT. This study aims to verify whether metformin can inhibit aortic calcification through the PI3K/AKT signaling pathway. Methods We first analyzed four microarray datasets to screen differentially expressed genes (DEGs) and signaling pathways related to CAVD. Then aortic valve samples were used to verify selected genes and pathways through immunohistochemistry (IHC) and western blot (WB) assays. Aortic valve interstitial cells (AVICs) were isolated from non-calcific aortic valves and then cultured with phosphate medium (PM) with or without metformin to verify whether metformin can inhibit the osteogenic differentiation and calcification of AVICs. Finally, we used inhibitors and siRNA targeting AMPK, NF-κB, and AKT to study the mechanism of metformin. Results We screened 227 DEGs; NF-κB and PI3K/AKT signaling pathways were implicated in the pathological mechanism of CAVD. IHC and WB experiments showed decreased AMPK and AKT and increased Bax in calcific aortic valves. PM treatment significantly reduced AMPK and PI3K/AKT signaling pathways, promoted Bax/Bcl2 ratio, and induced AVICs calcification. Metformin treatment ameliorated AVICs calcification and apoptosis by activating the PI3K/AKT signaling pathway. AMPK activation and NF-κB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin. Conclusions This study, for the first time, demonstrates that metformin can inhibit AVICs in vitro calcification by activating the PI3K/AKT signaling pathway; this suggests that metformin may provide a potential target for the treatment of CAVD. And the PI3K/AKT signaling pathway emerges as an important regulatory axis in the pathological mechanism of CAVD.

scholarly journals Network Pharmacology/Metabolomics-Based Validation of AMPK and PI3K/AKT Signaling Pathway as a Central Role of Shengqi Fuzheng Injection Regulation of Mitochondrial Dysfunction in Cancer-Related Fatigue

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Wei Guo ◽  
Shan Liu ◽  
Xinting Zheng ◽  
Zhiwei Xiao ◽  
Hanrui Chen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Muscle Cell ◽  
Herbal Medicines ◽  
Enrichment Analysis ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Cancer Therapies ◽  
Cancer Related Fatigue ◽  
Associated Proteins

Chinese herbal medicines have multiple targets and properties, and their use in multidisciplinary cancer therapies has consequently received increasing attention. Here, we have investigated the possible active ingredients associated with cancer-related fatigue (CRF) in the Shengqi Fuzheng Injection (SFI). In vitro cell models were used to measure the regulation effects of SFI on CRF. Metabolomic analysis was used to identify the potential genes and pathways in C2C12 mouse myoblasts treated with SFI, and the interaction of compounds and CRF targets was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified using immuno-blotting assays. The results showed that SFI significantly inhibited muscle cell apoptosis and increased the mitochondrial membrane potential of muscle cells. The network pharmacology analysis results identified 36 candidate compounds, and 244 potential targets were yielded by SFI, and they shared 10 key targets associated with cancer-related fatigue. According to the enrichment analysis and experimental validation, SFI might ameliorate muscle cell mitochondrial function by activating AMPK and inhibiting the PI3K/Akt signaling pathways, and the expression changes of mitochondrial metabolic enzymes MnSOD and apoptosis-associated proteins Bax and Bcl-2 were also triggered. The functions and mechanisms of SFI in anticancer-related fatigue were found here to be at least partly due to the targeting of the AMPK and PI3K/Akt signaling pathways, and this has highlighted new potential applications for network pharmacology when researching Chinese Medicines.

scholarly journals Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xianping Che ◽  
Jiangtao Zhan ◽  
Fan Zhao ◽  
Zunhe Zhong ◽  
Mianchuan Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Akt Signaling ◽  
Bladder Cancer Cell Line ◽  
Anticancer Efficacy ◽  
T24 Cells

Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.

scholarly journals IL-13 promotes in vivo neonatal cardiomyocyte cell cycle activity and heart regeneration

2019 ◽  
Vol 316 (1) ◽  
pp. H24-H34 ◽  
Author(s):  
Dylan J. Wodsedalek ◽  
Samantha J. Paddock ◽  
Tina C. Wan ◽  
John A. Auchampach ◽  
Aria Kenarsary ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Rna Sequencing ◽  
Akt Signaling ◽  
Heart Regeneration ◽  
Newborn Mice ◽  
Neonatal Cardiomyocyte

There is great interest in identifying signaling mechanisms by which cardiomyocytes (CMs) can enter the cell cycle and promote endogenous cardiac repair. We have previously demonstrated that IL-13 stimulated cell cycle activity of neonatal CMs in vitro. However, the signaling events that occur downstream of IL-13 in CMs and the role of IL-13 in CM proliferation and regeneration in vivo have not been explored. Here, we tested the role of IL-13 in promoting neonatal CM cell cycle activity and heart regeneration in vivo and investigated the signaling pathway(s) downstream of IL-13 specifically in CMs. Compared with control, CMs from neonatal IL-13 knockout (IL-13−/−) mice showed decreased proliferative markers and coincident upregulation of the hypertrophic marker brain natriuretic peptide ( Nppb) and increased CM nuclear size. After apical resection in anesthetized newborn mice, heart regeneration was significantly impaired in IL-13−/− mice compared with wild-type mice. Administration of recombinant IL-13 reversed these phenotypes by increasing CM proliferation markers and decreasing Nppb expression. RNA sequencing on primary neonatal CMs treated with IL-13 revealed activation of gene networks regulated by ERK1/2 and Akt. Western blot confirmed strong phosphorylation of ERK1/2 and Akt in both neonatal and adult cultured CMs in response to IL-13. Our data demonstrated a role for endogenous IL-13 in neonatal CM cell cycle and heart regeneration. ERK1/2 and Akt signaling are important pathways known to promote CM proliferation and protect against apoptosis, respectively; thus, targeting IL-13 transmembrane receptor signaling or administering recombinant IL-13 may be therapeutic approaches for activating proregenerative and survival pathways in the heart. NEW & NOTEWORTHY Here, we demonstrate, for the first time, that IL-13 is involved in neonatal cardiomyocyte cell cycle activity and heart regeneration in vivo. Prior work has shown that IL-13 promotes cardiomyocyte cell cycle activity in vitro; however, the signaling pathways were unknown. We used RNA sequencing to identify the signaling pathways activated downstream of IL-13 in cardiomyocytes and found that ERK1/2 and Akt signaling was activated in response to IL-13.

Sign in / Sign up

Export Citation Format

Share Document