scholarly journals Research on the mechanisms of taraxerol for the treatment of gastric cancer effect based on network pharmacology

2022 ◽  
Vol 36 ◽  
pp. 205873842110639
Author(s):  
Bingjie Huo ◽  
Yanru Song ◽  
Bibo Tan ◽  
Jianbo Li ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanism ◽  
Migration And Invasion ◽  
Network Pharmacology ◽  
Pentacyclic Triterpene ◽  
Pharmacological Analysis ◽  
Anti Cancer ◽  
Cancer Activity

Background: Modern pharmacological studies have shown that traditional Chinese medicine (TCM) Taraxacum mongolicum possesses anti-cancer activity. Taraxerol (TRX) is a pentacyclic triterpene isolated from T. mongolicum, which is widely used in clinical treatment, and its anti-cancer effects have been extensively studied. However, the effects and molecular mechanism of TRX in gastric cancer (GC) have not been fully explicated. Methods: We used public databases to derive information on potential targets of TRX and proteins related to GC. Also, STRING and R3.6.2 software were used to analyze the protein–protein interaction (PPI). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were done to explain the potential mechanism underlying the regulatory role of TRX in GC. The role of TRX in GC was verified by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, apoptosis analysis, Transwell assay, and wound healing assay, and the key signaling pathways were verified. Results: We identified 135 potential targets for the treatment of GC via network pharmacological analysis. GO and KEGG enrichment analysis showed that steroid hormone receptor activity and the PI3K/AKT signaling pathway were the biological processes and pathways with the highest degree of enrichment. Additionally, cellular experiments revealed that TRX inhibited the proliferation, migration, and invasion of GC cells as well as induced G1 phase arrest and apoptosis in GC cells. Conclusion: Here, we used multi-target and multi-pathway network pharmacological analysis to verify the anti-cancer activity of TRX in GC. Also, in vitro experimental data were used to derive the potential molecular mechanism.

scholarly journals An In Vitro Anti-Cancer Activity of Ocimum tenuiflorum Essential Oil by Inducing Apoptosis in Human Gastric Cancer Cell Line

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 784
Author(s):  
Wongwarut Boonyanugomol ◽  
Kamolchanok Rukseree ◽  
Pornpan Prapatpong ◽  
Onrapak Reamtong ◽  
Seung-Chul Baik ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Ags Cells ◽  
Anti Cancer ◽  
Ocimum Tenuiflorum ◽  
Cancer Activity

The effects of Ocimum tenuiflorum essential oil (OTEO) against gastric cancer remain unknown and merit investigation. In the present study, the anti-cancer activity of OTEO was examined in a human gastric cancer cell line (AGS). After OTEO treatment, AGS cell viability was determined by an MTT assay, and inhibition of metastasis was determined by cell migration and invasion assays. The expression of apoptosis-related genes in treated AGS cells was determined by qRT-PCR. OTEO significantly decreased AGS cell viability in a dose-dependent manner (IC50 163.42 µg/mL) and effectively inhibited cell migration and invasion. Morphological examination demonstrated that OTEO induced cell shrinkage, chromatin condensation, and fragmentation, which are considered typical morphologies of apoptotic cell death. Pro-apoptotic genes (TP53, BAX, and BAK) were significantly up-regulated, while anti-apoptotic genes (BCL-2 and BCL-xL) were significantly down-regulated after treatment with OTEO. In addition, significantly increased gene expression was detected for CASP8, CASP9, and CASP3 in AGS cells exposed to OTEO. GC-MS analysis demonstrated that the major compound of OTEO was caryophyllene (25.85%) and α-pinene (11.66%). This in vitro study demonstrates for the first time that OTEO has potential anti-gastric cancer activity and may induce apoptosis in AGS cells through extrinsic and intrinsic pathways.

scholarly journals BAG3 contributes to HGF-mediated cell proliferation, migration, and invasion via the Egr1 pathway in gastric cancer

2018 ◽  
Vol 105 (1) ◽  
pp. 63-75
Author(s):  
Jae Chang Lee ◽  
Sung Ae Koh ◽  
Kyung Hee Lee ◽  
Jae-Ryong Kim
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Protein Levels ◽  
Dependent Pathway

Introduction: Bcl2-associated athanogene 3 (BAG3) is elevated in several types of cancers. However, the role of BAG3 in progression of gastric cancer is unknown. Therefore, the present study aims to find out the role of BAG3 in hepatocyte growth factor (HGF)–mediated tumor progression and the molecular mechanisms by which HGF regulates BAG3 expression. Methods: BAG3 mRNA and protein were measured using reverse transcription polymerase chain reaction and Western blot in the 2 human gastric cancer cell lines, NUGC3 and MKN28, treated with or without HGF. The effects of BAG3 knockdown on cell proliferation, cell invasion, and apoptosis were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the in vitro 2-chamber invasion assay, and flow cytometry in BAG3 short hairpin RNA (shRNA)–transfected cells and control cells. The signaling pathways involved in BAG3 that are regulated by HGF were analyzed. The chromatin immunoprecipitation assay was used to determine binding of Egr1 to the BAG3 promoter. Results: BAG3 mRNA and protein levels were increased following treatment with HGF. HGF-mediated BAG3 upregulation increased cell proliferation and cell invasion; however, it decreased apoptosis. HGF-mediated BAG3 upregulation is regulated by an ERK and Egr1-dependent pathway. BAG3 may have an important role in HGF-mediated cell proliferation and metastasis in gastric cancer through an ERK and Egr1-dependent pathway. Conclusion: This pathway may provide novel therapeutic targets and provide information for further identification of other targets of therapeutic significance in gastric cancer.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

scholarly journals NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

2020 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Yan He ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Hippo Pathway ◽  
Critical Role ◽  
Xenograft Model ◽  
Migration And Invasion

Abstract Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

scholarly journals Molecular mechanism of the anti-lung cancer effect of Jin Ning Fang based on network pharmacology and experimental verification

2021 ◽  
Author(s):  
Chunxiao Wu ◽  
Qiquan Yu ◽  
Weizhen Shou ◽  
Kun Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanism ◽  
Mrna Level ◽  
A549 Cells ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Apoptosis Pathway ◽  
Protein Protein Interaction ◽  
Anti Cancer

Background: Jin Ning Fang (JNF) is widely used as an adjuvant therapy for lung cancer. However, its molecular mechanism against lung cancer is still unclear. Methods: The chemical compounds JNF were screened from the TCMSP database and its target proteins were then predicted. The genes related to lung cancer were collected from the CTD and DisGeNET databases. Next, targets were integrated with disease-related genes to obtain candidate genes. Functional enrichment and protein-protein interaction (PPI) analysis were also performed, followed by construction of pharmacological network. Meanwhile, Autodock was used to assess the affinity between targets and compound. Finally, the anti-cancer effect of JNF on lung cancer cells was detected and some predicted key genes was validated by using real-time PCR. Results: Twenty-five overlapping targets were obtained, and pathway analysis showed that JNF might exert its anti-cancer function by regulating some biological pathways, such as apoptosis pathway. PPI and pharmacological network revealed several core targets (such as AKT1, AR, and ESR1) and three compounds (quercetin, calcium carbonate, and beta-sitosterol). Then, beta-sitosterol had a high affinity with AKT1, AR, and ESR1. Further in vitro experiments confirmed that JNF could inhibit proliferation and promote apoptosis of A549 cells. The expression of FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ESR1 were significantly decreased, while mRNA level of AR and ANPEP were markedly increased after JNF treatment. Conclusion: JNF may exert anti-lung cancer effect through multiple targets and pathways, and identified genes may be used as potential biomarkers for diagnosis and treatment of lung cancer.

scholarly journals Chrysophanol Inhibits the Progression of Gastric Cancer by Activating NLRP3

2021 ◽  
Author(s):  
Hou Binfen ◽  
Li Zhao ◽  
Min Deng
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Antitumor Effects ◽  
Ags Cells ◽  
Anti Cancer ◽  
Colony Forming Assay

Abstract AimGastric cancer is one of the most common malignant tumors.Chrysophanol has been reported to have antitumor effects on a variety of cancers, but the role of chrysophanol in gastric cancer remains unclear. The aim of this study was to investigate the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of gastric cancer cells.MethodsMKN 28 and AGS cells were treatde with different concentrations of chrysophanol, then cell proliferation, migration,invasion and pyroptosis were decteed by CCK-8, Colony-forming assay, Wound Healing assay, Transwell and flow cytometry, respectively.Subsequently, NLRP3 siRNA was transfected into MKN 28 cells, cell proliferation pyroptosis, migration and invasion were reassessed in these transfected cells. The expression of caspase-1 and IL-1β in the downstream of NLRP3 was detected by qRT PCR and Western blot.ResultsChrysophanol significantly inhibited the proliferation of GC cells, promoted pyroptosis, inhibited cell migration and invasion, and up-regulated the expression level of NLRP3 inflammasome in GC cells. Silencing NLRP3 inhibited the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of MKN 28 cells. Chrysophanol plays an anti-cancer role through high expression of NLRP3.CoclusionsChrysophanol can inhibit the proliferation, migration and invasion of gastric cancer cells by regulating NLRP3, promote the death of gastric cancer cells, and play an anti-tumor role,which is a clinical strategy with great potential for the treatment of gastric cancer.

scholarly journals MicroRNA-491-5p inhibit gastric cancer development by targeting EMT, cell adhesion genes and IFITM2

2020 ◽  
Author(s):  
Zhijian Wei ◽  
Lixiang Zhang ◽  
Angqing Li ◽  
Chuanhong Li ◽  
Wenxiu Han ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Tumor Suppressor ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Different Types ◽  
High Level

Abstract Gastric cancer (GC) is one of the deadliest cancers in China. And, it can be regulated by MicroRNAs (miRNAs) generally. miR-491-5p function as a tumor suppressor in different types of cancer, but we still don’t know the role of miR-491-5p in gastric cancer. In this study, we found that high level of miR-491-5p caused a weak cell proliferation, migration and invasion abilities. In order to explore the role of miR-491-5p in vivo, we set a xenograft mouse model, and also found that high level of miR-491-5p suppressed tumor growth. Moreover, we found that miR-491-5p regulate the tumor development thought regulate the expression of EMT, cell adhesion genes and IFITM2. These data show that miR-491-5p function as a tumor suppressor in GC both in vitro and in vivo .

scholarly journals HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chenlong Song ◽  
Chongzhi Zhou
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Lung Metastasis ◽  
Essential Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Signaling Axis

Abstract Background Homeobox A10 (HOXA10) belongs to the HOX gene family, which plays an essential role in embryonic development and tumor progression. We previously demonstrated that HOXA10 was significantly upregulated in gastric cancer (GC) and promoted GC cell proliferation. This study was designed to investigate the role of HOXA10 in GC metastasis and explore the underlying mechanism. Methods Immunohistochemistry (IHC) was used to evaluate the expression of HOXA10 in GC. In vitro cell migration and invasion assays as well as in vivo mice metastatic models were utilized to investigate the effects of HOXA10 on GC metastasis. GSEA, western blot, qRT-PCR and confocal immunofluorescence experiments preliminarily analyzed the relationship between HOXA10 and EMT. ChIP-qPCR, dual-luciferase reporter (DLR), co-immunoprecipitation (CoIP), colorimetric m6A assay and mice lung metastasis rescue models were performed to explore the mechanism by which HOXA10 accelerated the EMT process in GC. Results In this study, we demonstrated HOXA10 was upregulated in GC patients and the difference was even more pronounced in patients with lymph node metastasis (LNM) than without. Functionally, HOXA10 promoted migration and invasion of GC cells in vitro and accelerated lung metastasis in vivo. EMT was an important mechanism responsible for HOXA10-involved metastasis. Mechanistically, we revealed HOXA10 enriched in the TGFB2 promoter region, promoted transcription, increased secretion, thus triggered the activation of TGFβ/Smad signaling with subsequent enhancement of Smad2/3 nuclear expression. Moreover, HOXA10 upregulation elevated m6A level and METTL3 expression in GC cells possible by regulating the TGFB2/Smad pathway. CoIP and ChIP-qPCR experiments demonstrated that Smad proteins played an important role in mediating METTL3 expression. Furthermore, we found HOXA10 and METTL3 were clinically relevant, and METTL3 was responsible for the HOXA10-mediated EMT process by performing rescue experiments with western blot and in vivo mice lung metastatic models. Conclusions Our findings indicated the essential role of the HOXA10/TGFB2/Smad/METTL3 signaling axis in GC progression and metastasis.

scholarly journals Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2149 ◽  
Author(s):  
Shuxian Yang ◽  
Yonghong Liao ◽  
Liyong Li ◽  
Xudong Xu ◽  
Li Cao
Keyword(s):  
Gastric Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mitochondrial Apoptosis ◽  
Apoptotic Pathway ◽  
Apoptotic Protein ◽  
Anti Cancer

The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the anti-cancer effect of Zey against gastric cancer both in vitro and in vivo, as well as the underlying mechanisms. We found that Zey inhibited gastric tumor growth, as demonstrated by in vitro gastric cancer cell lines and in a human gastric cancer xenograft mouse model. Furthermore, Zey induced substantial apoptosis through a mitochondrial apoptotic pathway, involving mitochondrial transmembrane potential loss, caspase-3 activation, anti-apoptotic protein downregulation, and pro-apoptotic protein upregulation. Notably, we revealed for the first time that Zey suppressed invasion and migration by wound healing and transwell chamber assays. Through Western blotting, we further explored the potential mechanism of Zey’s anti-cancer activity. We found that Zey downregulated the expression of matrix metalloproteinase 2/9 (MMP 2/9) and inhibited the phosphorylation of AKT and ERK. In short, Zey, which induced mitochondrial apoptosis and inhibited proliferation, migration, and invasion, may be developed as a novel drug for the treatment of gastric cancer.

scholarly journals The role of TRPV1 ion channels in the suppression of gastric cancer development

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Nannan Gao ◽  
Feng Yang ◽  
Siyuan Chen ◽  
Hanxing Wan ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Size ◽  
Peritoneal Dissemination ◽  
Migration And Invasion ◽  
Transient Receptor Potential Vanilloid ◽  
Aberrant Expression ◽  
Trpv1 Channels

Abstract Background Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association between transient receptor potential vanilloid receptor 1 (TRPV1) channels and gastric cancer (GC) has not yet been explored. Herein, we sought to determine the role of TRPV1 channels in the development of GC and to elucidate the underlying molecular mechanisms involved therein. Methods Immunohistochemistry, qPCR, Western blot, immunofluorescence assays were used to detect the mRNA and protein expression of TRPV1 in GC cells and tissues, and the clinical significance of TRPV1 in GC was also studied by clinicopathologic analysis. CCK8, colony formation, flow cytometry assays were used to detect the proliferation and survival of GC cells, while transwell assay was used to detect migration and invasion of GC cells in vitro. Tumor xenograft and peritoneal dissemination assays in nude mice were used to examine the role of TRPV1 in GC development in vivo. Results TRPV1 expression was significantly downregulated in human primary GC tissues compared to their adjacent tissues. The decreased expression of TRPV1 proteins in GC tissues was positively correlated with tumor size, histological grade, lymphatic metastasis, clinical stage, and was strongly correlated with poor prognosis of GC patients. Moreover, the expression of TRPV1 was closely correlated with Ki67, VEGFR, and E-cadherin, all of which are the well-known cancer markers for proliferation and metastasis. TRPV1 proteins were predominately expressed on the plasma membrane in several GC cell lines. TRPV1 overexpression blocked cell cycle at G1 phase to inhibit GC cell proliferation and attenuated migration and invasion of GC cells in vitro, but TRPV1 knockdown increased these parameters. TRPV1 significantly reduced gastric tumor size, number and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression in GC cells increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, while TRPV1 knockdown induced the opposite effects. Conclusions TRPV1 uniquely suppresses GC development through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival of human GC patients. Thus, TRPV1 upregulation and its downstream signaling may represent a promising target for GC prevention and therapy.

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