scholarly journals Leukemia inhibitory factor via the Toll-like receptor 5 signaling pathway involves aggravation of cachexia induced by human gastric cancer-derived 85As2 cells in rats

Oncotarget ◽  
2018 ◽  
Vol 9 (78) ◽  
pp. 34748-34764 ◽  
Author(s):  
Kiyoshi Terawaki ◽  
Yohei Kashiwase ◽  
Miaki Uzu ◽  
Miki Nonaka ◽  
Yumi Sawada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Human Gastric Cancer ◽  
Toll Like Receptor ◽  
Toll Like Receptor 5

scholarly journals Garcinol acts as an antineoplastic agent in human gastric cancer by inhibiting the PI3K/AKT signaling pathway

2020 ◽  
Vol 20 (1) ◽  
pp. 667-676
Author(s):  
Yuanyuan Zheng ◽  
Chuanyong Guo ◽  
Xiaoping Zhang ◽  
Xiaoli Wang ◽  
A'Ηuo Ma
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Antineoplastic Agent ◽  
Akt Signaling ◽  
Human Gastric Cancer ◽  
Akt Signaling Pathway

Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-Resistant Gastric Cancer SGC7901/DDP Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Dongmei Zhan ◽  
Tengyang Ni ◽  
Haibo Wang ◽  
Mengying Lv ◽  
Masataka Sunagawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
Resistance Index ◽  
Mtor Signaling ◽  
Control Group ◽  
Human Gastric Cancer ◽  
Cancer Resistance ◽  
Mtor Signaling Pathway ◽  
Expression Levels

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

Effects of Amygdalin on TLR4/NF-αB Signaling Pathway-Mediated Proliferation and Apoptosis of Gastric Cancer Cells

2021 ◽  
Vol 20 (1) ◽  
pp. 153-158
Author(s):  
Abulajiang Abudoukelimu ◽  
Xinhui Yang ◽  
Lei Ge ◽  
Xiangyue Zeng ◽  
Yin Shu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
B Cell Lymphoma ◽  
Toll Like Receptor ◽  
Gastric Cancer Cells ◽  
Toll Like Receptor 4 ◽  
Proliferation And Apoptosis ◽  
High Incidence Rate ◽  
Factor Α

Gastric cancer is a highly malignant tumor of the digestive tract with high incidence rate and mortality. In the present study, we have shown decreased cell proliferation, increased apoptosis, and expression of proinflammatory cytokines (Interleukin-6, Interleukin-1β, and Tumor necrosis factor-α) in gastric cancer cells MGC-803 by amygdalin. Also, amygdalin treatment significantly reduced expression of the mRNA and protein for B-cell lymphoma 2 protein, CyclinD1, toll-like receptor 4, and REL-associated protein involved in NF-κB heterodimer formation in MGC-803 cells. In summary, amygdalin inhibits the proliferation of gastric cancer cells MGC-803 and promotes cell apoptosis by regulating the toll-like receptor 4/ nuclear factor-kappa B signaling pathway.

scholarly journals MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Chunsheng Li ◽  
Jingrong Dong ◽  
Zhenqi Han ◽  
Kai Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

272 LEUKEMIA INHIBITORY FACTOR SIGNALING PATHWAY IN PIG PARTHENOGENETIC PLURIPOTENT CELLS

2009 ◽  
Vol 21 (1) ◽  
pp. 233
Author(s):  
T. A. L. Brevini ◽  
G. Pennarossa ◽  
S. Antonini ◽  
F. Gandolfi
Keyword(s):  
Molecular Markers ◽  
Signaling Pathway ◽  
Leukemia Inhibitory Factor ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Inhibitory Factor ◽  
Germ Layers ◽  
Undifferentiated State ◽  
Undifferentiated Cells

Leukemia inhibitory factor (LIF), its receptor heterodimer (LRβ-gp130), and the related signal transducer and activator of transcription-3 (STAT3) constitute a system controlling self-renewal and pluripotency of embryonic stem cells (ESC) in the mouse, where LIF withdrawal or direct inhibition of STAT3 causes ESC differentiation. By contrast, several studies have demonstrated that LIF is not required to maintain human ESC pluripotency. Scattered information is available in other species, and data on the role of LIF in pig ESC are scanty. The aims of the present study were (a) to characterize the expression profile of gp130, LRβ, and STAT3 in pig parthenogenetic cell lines (ppC), previously derived in our laboratory and shown to be positive for the main pluripotency related markers; (b) to evaluate the role of LIF pathway in maintaining the pluripotency of these cells. To this purpose, ppC were cultured as previously described (Brevini et al. 2007 Theriogenology 68, 206–214) and screened by RT-PCR for the two LIF receptor subunits (LRβ and gp130) and STAT3. Pig granulosa cells were used as positive controls. To better investigate the possible role of LIF in maintenance of pluripotency in ppC, the formation of embryoid bodies (EB) was induced in the presence or in the absence of the cytokine. Undifferentiated cells were cultured in hanging drops either with or without LIF for 12 days. The EB formation and the expression of molecular markers specific for the three germ layers was evaluated at the end of the differentiation period. Molecular analysis allowed us to detect transcription of STAT3, whereas no signal for LRβ and gp130 was detected in ppC. These results seem to indicate that LIF does not play a role in the maintenance of pluripotency in the pig. However, after removal of LIF, ppC routinely formed EB that expressed molecular markers specific for the three germ layers. On the other hand, when LIF was added to the differentiation medium, pig cells were unable to form EB. They kept proliferating in an undifferentiated state, and no expression of molecular markers specific for the three germ layers was detected. Moreover, when re-plated on inactivated feeder-layers, they formed distinct colonies that maintained expression of pluripotency markers. Our results show that a role of LIF in pluripotency maintenance through a classical LRβ-gp130 and STAT3 activation pathway is unlikely. However, interaction with an alternative nonclassical activation signaling pathway cannot be ruled out. Indeed, the presence of the cytokine in the medium used for differentiation experiments actively inhibited EB formation, indicating a possible role in preventing differentiation in the porcine species. Further studies are needed to elucidate these aspects. Supported by: PRIN2005; PRIN2006; First 2006; First2007.

scholarly journals MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway

2020 ◽  
Vol 217 (6) ◽  
Author(s):  
Liwei An ◽  
Pingping Nie ◽  
Min Chen ◽  
Yang Tang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Human Gastric Cancer ◽  
Hippo Signaling ◽  
Wild Type ◽  
Hippo Signaling Pathway ◽  
Phosphorylation Level ◽  
Signaling Axis ◽  
Importin Α

Hyperactivation of YAP has been commonly associated with tumorigenesis, and emerging evidence hints at multilayered Hippo-independent regulations of YAP. In this study, we identified a new MST4–YAP axis, which acts as a noncanonical Hippo signaling pathway that limits stress-induced YAP activation. MST4 kinase directly phosphorylated YAP at Thr83 to block its binding with importin α, therefore leading to YAP cytoplasmic retention and inactivation. Due to a consequential interplay between MST4-mediated YAP phospho-Thr83 signaling and the classical YAP phospho-Ser127 signaling, the phosphorylation level of YAP at Thr83 was correlated to that at Ser127. Mutation of T83E mimicking MST4-mediated alternative signaling restrained the activity of both wild-type YAP and its S127A mutant mimicking loss of classical Hippo signal. Depletion of MST4 in mice promoted gastric tumorigenesis with diminished Thr83 phosphorylation and hyperactivation of YAP. Moreover, loss of MST4–YAP signaling was associated with poor prognosis of human gastric cancer. Collectively, our study uncovered a noncanonical MST4–YAP signaling axis essential for suppressing gastric tumorigenesis.

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