scholarly journals Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5955
Author(s):  
Na-Ri Lee ◽  
Da-Yeah Kim ◽  
Hua Jin ◽  
Ruoyu Meng ◽  
Ok Hee Chae ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Animal Experiments ◽  
Hdac Inhibitors ◽  
Dependent Manner ◽  
Akt Inhibitor ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Protein Levels

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Histone deacetylase (HDAC) inhibitors are a new class of cytostatic agents available for the treatment of various cancers and diseases. Although numerous clinical and pre-clinical trials on the anticancer effects of panobinostat have been conducted, only a few reports have investigated its efficacy in gastric cancer. The present study aimed to investigate the effects of panobinostat in gastric cancer cells. Panobinostat significantly inhibited the cell viability and proliferation of the gastric cancer cell lines SNU484 and SNU638 in a dose-dependent manner; it reduced the colony-forming ability of these cells. Moreover, it induced apoptosis as indicated by increased protein levels of cleaved poly ADP-ribose polymerase and cleaved caspase-3. Panobinostat induced the G2/M cell cycle arrest in SNU484 and SNU638 cells and subsequently decreased the G2/M phase regulatory-associated protein expression of p-Wee1, Myt1, and Cdc2. Furthermore, panobinostat significantly inhibited the metastasis of SNU484 and SNU638 cells by regulating the expression of MMP-9 and E-cadherin. Further, it decreased the protein levels of p-Akt and forkhead box protein M1 (FOXM1). These effects were reversed by the Akt agonist SC79 and were accelerated by the Akt inhibitor LY2940002. Moreover, tumor growth in xenograft animal experiments was suppressed by panobinostat. These results indicated that panobinostat inhibits the proliferation, metastasis, and cell cycle progression of gastric cancer cells by promoting apoptosis and inactivating Akt/FOXM1 signaling. Cumulatively, our present study suggests that panobinostat is a potential drug for the treatment of gastric cancer.

scholarly journals Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4709 ◽  
Author(s):  
Seong-Hun Kim ◽  
Hua Jin ◽  
Ruo Yu Meng ◽  
Da-Yeah Kim ◽  
Yu Chuan Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Hippo Pathway ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Protein Levels ◽  
Tumor Tissues ◽  
The Hippo Pathway

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.

scholarly journals Ailanthone induces G2/M cell cycle arrest and apoptosis of SGC-7901 human gastric cancer cells

2017 ◽  
Vol 16 (5) ◽  
pp. 6821-6827 ◽  
Author(s):  
Yuxin Chen ◽  
Ling Zhu ◽  
Xi Yang ◽  
Cheng Wei ◽  
Chuanrong Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Cycle Arrest

scholarly journals Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis

2017 ◽  
Vol 14 (1) ◽  
pp. 416-422 ◽  
Author(s):  
Green Kim ◽  
Tae-Hyoun Kim ◽  
Eun-Ha Hwang ◽  
Kyu-Tae Chang ◽  
Jung Joo Hong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Withaferin A ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Cycle Arrest

scholarly journals Gramicidin inhibits human gastric cancer cell proliferation, cell cycle and induced apoptosis

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Tingting Chen ◽  
Yong Wang ◽  
Yang Yang ◽  
Kaikai Yu ◽  
Xiangliao Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
High Morbidity ◽  
Peptide Antibiotic ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells

Abstract Background Gastric cancer is a common malignant tumor with high morbidity and mortality worldwide, which seriously affects human health. Gramicidin is a short peptide antibiotic which could be used for treating infection induced by bacteria or fungi. However, the anti-cancer effect of gramicidin on gastric cancer cells and its underlying mechanism remains largely unknown. Results Gastric cancer cells SGC-7901, BGC-823 and normal gastric mucosal cells GES-1 were treated with different concentrations of gramicidin respectively. The results of CCK-8 experiment revealed cellular toxicity of gramicidin to cancer cells while cell colony formation assay showed that gramicidin significantly inhibited the proliferation of gastric cancer cells, but had little effect on normal gastric mucosal cells. In addition, the wound healing assay showed that gramicidin inhibited the migration of SGC-7901 cell. Meanwhile, apoptosis and cell cycle analysis revealed that gramicidin induced cell apoptosis with G2/M cell cycle inhibition. Furthermore, western blot analysis demonstrated that gramicidin down-regulated the expression of cyclinD1 and Bcl-2 as well as the FoxO1 phosphorylation. Conclusions The current study illustrated the anti-tumor activity of gramicidin on gastric cancer cells, providing a possibility for gramicidin to be applied in clinical practice for the treatment of gastric cancer.

scholarly journals Bufalin inhibits the growth and epithelial to mesenchymal transition of human gastric cancer cells via modulation of MEK/ERK pathway

2021 ◽  
Vol 16 (1) ◽  
pp. 27-33
Author(s):  
Yi Zhou ◽  
Liguo Wang ◽  
Hui Lin ◽  
Yunxia Wang ◽  
Kezhu Hou
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Cycle Arrest

This study was designed to evaluate the anti-cancer effects of bufalin against the human gastric cancer cells and unveil the underlying mechanism. The results showed that bufalin inhibited the proliferation and colony formation of the MGC-803 gastric cancer cells and exhibited an IC50 of 10 μM. These antiproliferative effects were found to be due to the induction of G2/M cell cycle arrest. The G2/M cell cycle arrest was also concomitant with inhibition of cdc2, cdc25 and cyclin B1. Furthermore, bufalin suppressed the epithelial-to-mesenchymal transition, migration, and invasion of the MGC-803 gastric cancer cells. The Western blot analysis revealed that bufalin exerted its effects via deactivation of EK/ERK signaling pathway. Taken together, these results suggest the potential of bufalin as the lead molecule for the development of chemotherapy for gastric cancer.  

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

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