Investigating the Effects of Salvia chorassanica Bunge and Shoot Extracts on Gastric Cancer Cells: Evidence of Different Behavior on Various Tumor Grades

Background: Different Salvia species have demonstrated anti-proliferative effects on various cancer cells. Owing to the poor literature on the anti-proliferative effects of Salvia species on gastric cancer cells, present study was conducted to determine the anticancer effects of a local Iranian Salvia, Salvia chorassanica, on two different gastric cell lines. Methods: Root, stem and leaf extract of Salvia chorassanica were prepared through maceration method and were then used to treat the AGS and MKN-45 cell lines in different concentrations. MTT assay was employed to determine the toxicity of all the types of extracts on the two studied cell lines. The expression of Bax, Bcl-2, Caspase3, MMP2 and MMP9 genes were determined through reverse transcription Real time PCR (RT-PCR). Results: Bunge and shoot extracts demonstrated toxicity in both cell lines which were more considerable in AGS cells treated with root extract. In contrary to AGS cells, Caspase3 gene was up-regulated in all types of treatment while the MMP2 and MMP9 genes were down-regulated (p-value<0.001). Except of the MKN-45 cells treated with leaf extract, Bax/Bcl-2 expression ratio was decreased in the treatment with all types of Salvia chorassanica extracts (p-value<0.001). Conclusion: Remarkable low IC50 concentration of root extract in MKN-45 cell line is indicating the significant cytotoxicity of Salvia chorassanica against gastric cancer cells. Moreover, gene expression analysis in MKN-45 needs further confirmation on the potential anti-metastatic roles of leaf and root extracts in higher grades of gastric cancer.

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ANXA2 Silencing Inhibits Proliferation, Invasion, and Migration in Gastric Cancer Cells

Journal of Oncology ◽

10.1155/2019/4035460 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Rui Xie ◽

Jia Liu ◽

Xuefeng Yu ◽

Chunfeng Li ◽

Yufeng Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Biological Behavior ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Ags Cells ◽

Invasion And Migration ◽

Ags Cell Line ◽

And Migration

Annexin A2 (ANXA2) has been well known to associate with the progress of malignant tumor. However, the biological behavior of ANXA2 in gastric cancer (GC) remains unclear. We made a hypothesis in transcriptome level from TCGA datasets. Then, we used immunohistochemical staining to quantify the expression level of ANXA2 protein in GC tissues compared with adjacent tissues. Quantitative real-time PCR and western blot were used for analyzing ANXA2 expression in human GC (SGC-7901, MKN-45, BGC-823, and AGS) cell lines. We investigated the effect of a lentivirus-mediated knock-down of ANXA2 on the proliferation, invasion and migration of gastric cancer AGS cells. Cell proliferation was examined by MTT and colony formation tests. Cell apoptosis and cycle were measured by flow cytometry. Migration and invasion were detected by transwell assay. We found that high expression of ANXA2 can increase the mobility of cancer cells from TCGA datasets. ANXA2 was upregulated in GC tissues compared with adjacent tissues. AGS cell line displayed significantly higher expression of ANXA2 among the four GC cell lines. In addition, ANXA2 silencing led to a weakened ability of proliferation, invasion, and migration in GC cells; targeting of ANXA2 may be a potential therapeutic strategy for GC patients.

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Effects of Epinephrine on Gastric Adenocarcinoma and Brain Glioblastoma Cancer Cells

10.21203/rs.3.rs-443068/v1 ◽

2021 ◽

Author(s):

Majid Malekzadeh Shafaroudi ◽

Nourollah Rezaei ◽

Abbas Noori ◽

Hooman Zarei ◽

Javad Akhtari ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Gastric Adenocarcinoma ◽

Cell Lines ◽

P Value ◽

Adhesion Assay ◽

Human Gastric Cancer ◽

Ags Cells ◽

Brain Tumor Cell ◽

The Right

Abstract Introduction: Gastric cancer is the third cause of death in all malignancies and the fifth most common neoplasm resulting from a combination of specific genetic alteration and environmental factors. Chronic stress can also promote brain tumor cell proliferation and leads to brain metastasis highly resistant to chemotherapy. Catecholamines, norepinephrine, and epinephrine impact neurochemistry and endocrine and immune system functions. The present study investigated the effect of different epinephrine concentrations and β-adrenergic receptor antagonists (propranolol) on proliferation, viability, and adhesion of gastric adenocarcinoma and brain glioblastoma cells.Material and methods: The human gastric cancer AGS cells and glioblastoma, U87 cell lines were obtained from the Iranian Biological Resource Center (Tehran, Iran) and cultured in RPMI-1640 culture medium supplements. The studied cells were categorized into the nine groups following treatment with epinephrine and propranolol. Wound healing assay (proliferation), Adhesion assay, and cell viability were performed on each group. Graph Pad Prism 6 was used for the statistical analysis. Results: Proliferation, Viability, cytotoxicity, and adhesion of both cell lines changed under epinephrine agonism in the presence and absence of propranolol (P value<0.001). Epinephrine enhanced the proliferation of both AGS and U87 cells in physiological concentrations, decreased adhesion and viability, and increased cytotoxicity in pharmacological concentrations.Conclusion: Using a combination of epinephrine and chemotherapy agents in the right stage of developing tumors may have more substantial effects on destroying cancer cells, obtaining the patient's recovery with less repetition of chemotherapy sessions, and curing high-grade cancer tumors.

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Laurocerasus officinalis Roem. fruit extract induces cell death through caspase mediated apoptosis in gastric cancer cell lines

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0378 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Nihal Karakaş ◽

Mehmet Evren Okur ◽

Nurşah Öztunç ◽

Derya Çiçek Polat ◽

Ayşe Esra Karadağ

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Cancer Cell Lines ◽

Gastric Cancer Cells ◽

Fruit Extract ◽

Anticancer Effects ◽

Gastric Cancer Cell Lines

AbstractObjectivesLaurocerasusofficinalis Roem. fruits are traditionally used for several health problems. Although there are some studies about its antiproliferative effects on different cancer cells, no study was reported about its potential therapeutic efficacy against gastric cancers which is the most malignant disease in the digestive system with high morbidity and mortality.MethodsThis study was aimed to evaluate L. officinalis fruit extract phytochemical contents as well as to compare anticancer effects on gastric cancer cells. The antioxidant activities were determined by ABTS and DPPH assays. Anticancer effects were measured by cell viability assays, then apoptotic proteins were analyzed by western blotting and flow cytometry.ResultsLaurocerasus officinalis fruit methanol extract showed moderate antioxidant activity by ABTS• and DPPH• assays. Significant cytotoxic activities and caspase mediated apoptosis were detected in the extract treated MKN-45 and AGS gastric cancer cells respectively while sparing healthy cells.ConclusionOur results showed that the L. officinalis Roem. extract has significant anticancer efficacy on gastric cancer cell lines; therefore, it can be further studied to determine its potential therapeutic components.

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

Current Molecular Medicine ◽

10.2174/1566524020666201120113538 ◽

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.

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Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽

10.3390/cells10071820 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1820

Author(s):

Chengcheng Hao ◽

Yuxin Cui ◽

Jane Lane ◽

Shuqin Jia ◽

Jiafu Ji ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Prognostic Value ◽

Splice Variants ◽

Tnm Staging ◽

Migration And Invasion ◽

Ros Production ◽

Gastric Cancer Cells ◽

Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

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Sevoflurane represses the migration and invasion of gastric cancer cells by regulating forkhead box protein 3

Journal of International Medical Research ◽

10.1177/03000605211005936 ◽

2021 ◽

Vol 49 (4) ◽

pp. 030006052110059

Author(s):

Fangfang Yong ◽

Hemei Wang ◽

Chao Li ◽

Huiqun Jia

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cell Lines ◽

Migration And Invasion ◽

Control Group ◽

Gastric Cancer Cells ◽

Cell Migration And Invasion ◽

Forkhead Box ◽

Induced Apoptosis

Objective Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells. Methods GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively. Results FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells. Conclusions Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.

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

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02497-1 ◽

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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IFT80 Improves Invasion Ability in Gastric Cancer Cell Line via ift80/p75NGFR/MMP9 Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms19113616 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3616 ◽

Cited By ~ 3

Author(s):

Rui Wang ◽

Xiaoyan Deng ◽

Chengfu Yuan ◽

Hongmei Xin ◽

Geli Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Reverse Transcription ◽

Gastric Cancer Cell ◽

Gastric Cancer Cells ◽

Quantitative Reverse Transcription Pcr ◽

Reverse Transcription Pcr ◽

Gastric Cancer Cell Lines

The assembly and maintenance of cilia depend on intraflagellar transport (IFT) proteins, which play an important role in development and homeostasis. IFT80 is a newly defined IFT protein and partial mutation of IFT80 in humans causes diseases such as Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III, both characterized by abnormal skeletal development. However, the role and mechanism of IFT80 in the invasion of gastric cancer is unknown. We established SGC-7901 and MKN-45 gastric cancer cell lines that stably overexpressed IFT80, as verified by quantitative reverse transcription-PCR, Western blot, and immunofluorescence. Matrix metalloproteinase-9 (MMP9) plays an important role in tumor invasion, and its expression was assessed by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence. The invasion ability of IFT80 on SGC-7901 and MKN-45 cells was examined by the Matrigel invasion assay. The relationship between p75NGFR, and the p75NGFR antagonists, PD90780 and IFT80, were detected by quantitative reverse transcription-PCR and Western blotting. We first detected an IFT80 expression pattern, and found that IFT80 was highly expressed in gastric cancer clinical samples. Overexpression of IFT80 in the gastric cancer cell lines, SGC-7901 and MKN-45, led to lengthening cilia. Additionally, overexpression of IFT80 significantly improved proliferation and invasion, but inhibited apoptosis, in gastric cancer cells. We further found that overexpression of IFT80 increased p75NGFR and MMP9 mRNA and protein expression. Treatment with the p75NGFR antagonist PD90780 inhibited the increased invasion ability resulting from overexpression of IFT80 in SGC-7901 and MKN-45 gastric cancer cells. Thus, these results suggest that IFT80 plays an important role in invasion of gastric cancer through regulating the ift80/p75NGFR/MMP9 signal pathways.

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miR-335-5p Suppresses Gastric Cancer Progression by Targeting MAPK10

10.21203/rs.3.rs-52496/v1 ◽

2020 ◽

Author(s):

Yi Gao ◽

Yanfeng Wang ◽

Xiaofei Wang ◽

Changan Zhao ◽

Fenghui Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Progression ◽

Target Gene ◽

Luciferase Reporter ◽

Gastric Cancer Cells ◽

Aberrant Expression ◽

Related Target

Abstract Background: In recent years, many microRNAs(miRNAs) involved in cancer progression. The aberrant expression of miR-335-5p in tumorigenesis has been demonstrated. The present study aimed to investigate the molecular mechanisms underlying miR-335-5p- regulated MAPK10 expression in human gastric cancer（GC）.Methods: The quantitative real-time PCR was used to study the level of miR-335-5p expression in gastric cancer cell lines and tissues. Subsequently, the MTT and cloning formation assays were used to detect cell proliferation, while transwell and wound-healing assays were used to identify invasion and migration of the gastric cancer cells. The correlation between the miR-335-5p and the cell cycle-related target gene mitogen‑activated protein kinase 10 (MAPK10) in gastric cancer was analyzed based on the website. In addition, the target gene of miR-335-5p was detected by luciferase reporter assay, qRT-PCR, and western blotting.Results: The miR-335-5p level was down-regulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited proliferation, migration of gastric cancer cells, and induced apoptosis. During the G1/S phase, miR-335-5p arrested the cycle of gastric cancer cells in vitro. The correlation between the miR-335-5p and the cell cycle-related target gene MAPK10 in GC was analyzed, MAPK10 was directly targeted by the miR-335-5p.Conclusion: These data suggested that miR-335-5p acts as a tumor suppressor, and go through the MAPK10 to inhibit the GC progression.

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Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines

Biomolecules ◽

10.3390/biom9120833 ◽

2019 ◽

Vol 9 (12) ◽

pp. 833 ◽

Cited By ~ 2

Author(s):

Valentina Pagliara ◽

Rosarita Nasso ◽

Paola Di Donato ◽

Ilaria Finore ◽

Annarita Poli ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cell Lines ◽

Interleukin 6 ◽

Protective Role ◽

Citrus Limon ◽

Human Gastric Cancer ◽

Ags Cells ◽

Industrial Processing

Among plant polyphenols, lemon peels extract (LPE) from the residues of the industrial processing of lemon (Citrus limon) shows anti-proliferative properties in cancer cells and anticholinesterase activity. In this study, we analyze the anti-cancer properties of LPE on migration and invasiveness in MKN-28 and AGS human gastric cancer cell lines either in the absence or presence of the pro-inflammatory cytokine IL-6. We find that the pretreatment with non-cytotoxic concentrations (0.5–1 μg/ml of gallic acid equivalent) of LPE inhibits interleukin-6 (IL-6)-induced cell migration and invasiveness in MKN-28 and AGS cells, as analyzed by wound and matrigel assays. Pretreatment with LPE is able to prevent either IL-6-induced matrix metalloproteinases (MMP)-9/2 activity, as assessed by gel zymography, or mRNA and protein MMP-9/2 expression, as evaluated by qPCR and Western blotting analysis, respectively. These LPE effects are associated with an IL-6-dependent STAT3 signaling pathway in MKN-28 and AGS cells. Furthermore, LPE shows acetylcholinesterase inhibitory activity when assayed by the Ellman method. In conclusion, our results demonstrate that LPE reduces the invasiveness of gastric MKN-28 and AGS cancer cells through the reduction of IL-6-induced MMP-9/2 up-regulation. Therefore, these data suggest that LPE exerts a protective role against the metastatic process in gastric cancer.

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