scholarly journals Synergistic Effect of Zuo Jin Wan on DDP-Induced Apoptosis in Human Gastric Cancer SGC-7901/DDP Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qing-Feng Tang ◽  
Qing Ji ◽  
Yan-Yan Qiu ◽  
Ai-Li Cao ◽  
Yang-Feng Chi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cytochrome C ◽  
Synergistic Effect ◽  
Human Cancer ◽  
Xenograft Model ◽  
Human Gastric Cancer ◽  
Caspase 9 ◽  
Induced Apoptosis

A traditional Chinese medicine (TCM) formula, Zuo Jin Wan (ZJW), has been found as an anticancer drug in human cancer. In this study, we investigated the synergistic effect of ZJW extracts on DDP-induced apoptosis in human gastric cancer SGC-7901/DDP cells. Our results demonstrated that ZJW extracts could increase the sensitivity of SGC-7901/DDP cells to DDP by increasing the concentration of DDP in cytoplasm and enhance the proapoptosis of DDP by upregulating the JNK and Bax expression, downregulating the Bcl-2 expression, increasing the accumulation of Cytochrome C in cytoplasm, and promoting the activities of caspase-3 and caspase-9.In vivo, ZJW extracts enhanced the inhibiting effect of DDP on tumor growth in SGC-7901/DDP xenograft model and upregulated the expression of p-JNK and Bax but downregulated the Bcl-2 expression in xenograft tumors. In conclusion,in vitroandin vivo, ZJW extracts could enhance the proapoptotic effect of DDP by promoting the activation of JNK and the expression of Bcl-2, inhibiting the Bax expression, followed by increasing the release of Cytochrome C from mitochondria to cytoplasm, and finally activating the caspase cade reaction. Our results implied that ZJW might serve as a synergistic drug with chemotherapeutic drugs DDP in the treatment of gastric cancer.

scholarly journals Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Beibei Chen ◽  
Sai-Qi Wang ◽  
Jinxi Huang ◽  
Weifeng Xu ◽  
Huifang Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Gastric Cancer Cells ◽  
And Migration ◽  
Induced Apoptosis ◽  
Gastric Cancer Patients

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/β-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

scholarly journals Berberine Suppressed Tumor Growth through Regulating Fatty Acid Metabolism and Triggering Cell Apoptosis via Targeting FABPs

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Lingli Li ◽  
Ze Peng ◽  
Qian Hu ◽  
Lijun Xu ◽  
Xin Zou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Fatty Acid ◽  
Protein Expression ◽  
Cell Viability ◽  
Human Gastric Cancer ◽  
Dependent Manner ◽  
Xenograft Models ◽  
Induced Apoptosis

Aim. To further investigate the mechanism behind the antitumor properties of berberine regarding lipid metabolism. Methods. Cell viability, proliferation, and apoptosis assays were performed to determine the antigrowth effects of berberine in vitro. Ectopic xenograft models in Balb/c nude mice were established to determine the antitumor effects of berberine in vivo. Results. Berberine inhibited cell viability and proliferation of MGC803 human gastric cancer cell lines in a time- and dose-dependent manner. Berberine induced apoptosis of MGC803 and increased the apoptotic rate with higher doses. Berberine induced the accumulation of fatty acid of MGC803 and suppressed the protein expression of FABPs and PPARα. The FABP inhibitor BMS309403 recapitulated the effects of berberine on MGC803 cells. In the xenograft model, berberine significantly decreased the tumor volume and tumor weight and induced apoptosis in tumor tissues. Berberine significantly elevated the fatty acid content and inhibited the expression of FABPs and PPARα in the MGC803 xenograft models. Conclusion. Berberine exerted anticancer effects on human gastric cancer both in vitro and in vivo by inducing apoptosis, which was due to the reduced protein expression of FABPs and the accumulation of fatty acid.

scholarly journals CARM1 Promotes Gastric Cancer Progression by Regulating TFE3 Mediated Autophagy Enhancement via Cytoplasmic AMPK-mTOR and Nuclear CARM1-TFE3 Signaling Pathways

2021 ◽  
Author(s):  
Suzhen Yang ◽  
Jing Zhang ◽  
Di Chen ◽  
Jiayi Cao ◽  
Ying Zheng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Er Stress ◽  
Signaling Pathways ◽  
Nuclear Translocation ◽  
Xenograft Model ◽  
Induced Apoptosis

Abstract Background: The role of CARM1 in tumors is contradictory. It acts as an oncogene in most kinds of cancers while inhibits the progression of liver and pancreatic cancers. CARM1 has recently been reported to regulate autophagy, which is also context-dependent. However, the effect of CARM1 on gastric cancer has not been studied. We aimed to explore whether CARM1 was involved in the progression of gastric cancer by regulating autophagy.Methods: The clinical values of CARM1 and autophagy in gastric cancer were determined by immunohistochemistry and qRT-PCR. Transmission electron microscopy, immunofluorescence and western blotting were applied to recognize autophagy. The role of CARM1 in gastric cancer was investigated by CCK8, colony formation and flow cytometry assays in vitro and xenograft model in vivo. Immunoprecipitation assay was performed to illustrate the interaction of CARM1 and TFE3.Results: CARM1 was upregulated in clinical GC tissues and cell lines, and higher CARM1 expression predicted worse prognosis. CARM1 enhanced GC cell proliferation, facilitated G1-S transition and inhibited ER stress-induced apoptosis by regulating autophagy. Importantly, the treatment of CARM1 inhibitor rescued the tumor-promoting effects of CARM1 both in vitro and in vivo. Furthermore, we proved CARM1 heightened TFE3 nuclear translocation to induce autophagy via cytoplasmic AMPK-mTOR and nuclear CARM1-TFE3 signaling pathways.Conclusion: CARM1 promoted GC cell proliferation, accelerated G1-S transition and reduced ER stress-induced apoptosis by regulating autophagy. Mechanically, CARM1 triggered autophagy by facilitating TFE3 nuclear translocation via AMPK-mTOR and CARM1-TFE3 signaling pathways.

scholarly journals Silencing of EphA2 inhibits invasion of human gastric cancer SGC-7901 cells in vitro and in vivo

Neoplasma ◽  
2012 ◽  
Vol 59 (01) ◽  
pp. 105-113 ◽  
Author(s):  
W. Yuan ◽  
Z. Chen ◽  
Z. Chen ◽  
S. Wu ◽  
J. Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Human Gastric Cancer

scholarly journals Hypermethylation of DHRS3 as a Novel Tumor Suppressor Involved in Tumor Growth and Prognosis in Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Sha Sumei ◽  
Kong Xiangyun ◽  
Chen Fenrong ◽  
Sun Xueguang ◽  
Hu Sijun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Human Cancer ◽  
Methylation Status ◽  
Ectopic Expression ◽  
Survival Times

Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

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 Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

2020 ◽  
Author(s):  
Guiqing Zhou ◽  
Jianhui Liu ◽  
Xiangyang Li ◽  
Yujian Sang ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Silica Nanoparticles ◽  
Caspase 3 ◽  
Reproductive Toxicity ◽  
Control Group ◽  
Caspase 9 ◽  
Protein Expressions ◽  
Underlying Mechanisms

Abstract Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

2016 ◽  
Vol 40 (7) ◽  
pp. 770-778 ◽  
Author(s):  
Hao Nie ◽  
Yu Wang ◽  
Yong Qin ◽  
Xing-Guo Gong
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Oleanolic Acid ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals Increased Thioredoxin-1 Expression Promotes Cancer Progression and Predicts Poor Prognosis in Patients with Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Wenjing Shang ◽  
Zhongdong Xie ◽  
Fengying Lu ◽  
Daoquan Fang ◽  
Tianbin Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Antitumor Effects ◽  
Thioredoxin 1

Background. Thioredoxin-1 (Trx-1) is a small redox protein, which plays an important role in many biological processes. Although increased expression of Trx-1 in various solid tumors has been reported, the prognostic significance and function of Trx-1 in human gastric cancer (GC) are still unclear. Here, we investigated the clinical and prognostic significance of Trx-1 expression and the function and mechanism of Trx-1 in human GC. Methods. We analyzed Trx-1 mRNA expression from the GEO database and Trx-1 protein expression in 144 GC tissues using immunohistochemistry. Effects of Trx-1 on GC cell were assessed in vitro and in vivo through Trx-1 knockdown or overexpression. The antitumor effects of the Trx-1 inhibitor, PX-12, on GC cells were investigated. PTEN and p-AKT expressions were evaluated by Western blotting. Results. Increased Trx-1 expression was found in GC tissues and associated with poor prognosis and aggressive clinicopathological characteristics in patients with GC. High Trx-1 expression predicted poor prognosis, and its expression was an independent prognostic factor for overall survival of GC patients. Knockdown of Trx-1 expression inhibited GC cell growth, migration, and invasion in vitro and tumor growth and lung metastasis in vivo. Conversely, overexpression of Trx-1 promoted GC cell growth, migration, and invasion. We also found that PX-12 inhibited GC cell growth, migration, and invasion. Overexpression of Trx-1 caused a decrease in PTEN and increase in p-AKT levels whereas silencing Trx-1 caused an increase in PTEN and decrease in p-AKT levels in GC cells. Inhibition of AKT signaling pathway by MK2206 also inhibited GC cell growth, migration, and invasion. Conclusion. Our results indicate that Trx-1 may be a promising prognostic indicator and therapeutic target for GC patients.

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