Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil

Abstract Background Gastric cancer is a common gastrointestinal cancer characterized by poor prognosis and chemoresistance. Docetaxel and 5-fluorouracil (5-FU) are frequently used for the treatment of gastric cancer. Despite their potent anti-cancer effects, chemoresistance occurs in metastatic gastric cancer. Metformin, a popular anti-diabetic drug, has been proven to have potent anticancer effects on gastrointestinal cancers. Here, we aim to improve this chemotherapy agents’ efficacy by pretreatment with metformin. Methods The AGS gastric cancer cell line were pretreated with three different sub-toxic concentration of metformin and then treated with various concentrations of 5-FU and docetaxel.The anticancer effects of the combination of metformin with the chemotherapy agents were determined using clonogenic assay and DAPi staining. We used real-time PCR to evaluate Gli1, Gli2, and TWIST1 mRNA expression levels in the gastric cancer cells. Also, the expression of the Shh protein was assessed using immunocytochemistry. Results Here, we found that metformin sensitized the gastric cancer cells to chemotherapy. The combination treatments were more effective in reducing the number of cancer colonies compared to 5-FU or docetaxel alone. The combination of metformin with 5-FU or docetaxel significantly reduced the number of cells expressing the Shh protein compared to the 5-FU alone or docetaxel alone. Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1, Gli2, and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone. Conclusion Overall, our data strongly support an important role for metformin as an enhancer of the efficacy of chemotherapeutic agents against gastric cancer.

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Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line

Genes & Genomics ◽

10.1007/s13258-021-01151-7 ◽

2021 ◽

Author(s):

Juan Luo ◽

Luyan Bai ◽

Jun Tao ◽

Yu Wen ◽

Mingke Li ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Line ◽

Molecular Mechanism ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

H Pylori

Abstract Background Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molecular mechanism by which VacA induces autophagy is largely unknown. Objective We aimed to explore the molecular mechanism of autophagy induced by H. pylori in gastric cancer cells and the effect of autophagy on the survival of gastric cancer cells. Methods The autophagy of human gastric cancer cell line SGC7901 was detected by Western blot and RT-PCR in the treatment of VacA protein of H. pylori. The relationship between autophagy and reactive oxygen species (ROS) in the proliferation of gastric cancer cells were studied by gene expression silences (siRNA) and CM-H2DCFDA (DCF) staining. Results The results showed that VacA protein secreted by H. pylori in the supernatant stimulated autophagy in SGC7901 cells. After VacA protein treatment, the mRNA expressions of BECN1, ATG7 and PIK3C3, were up-regulated. ATG7 silencing by siRNA inhibited VacA-induced autophagy. Furthermore, our data demonstrated that VacA protein increased ROS levels. Addition of the antioxidant N-acetyl-l-cysteine (NAC) suppressed the levels of ROS, leading to inhibition of autophagy. Conclusions H. pylori VacA is a key toxin that induces autophagy by increased ROS levels. And our findings demonstrated that VacA significantly inhibited proliferation in SGC7901 cells.

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Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line

International Journal of Molecular Sciences ◽

10.3390/ijms22147698 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7698

Author(s):

Sara Peri ◽

Alessio Biagioni ◽

Giampaolo Versienti ◽

Elena Andreucci ◽

Fabio Staderini ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Line ◽

Cancer Cell ◽

Intracellular Signaling ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Tumor Evolution ◽

Selective Growth Advantage

Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes; among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability.

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Pulsed Magnetic Fields Cause hes1 and hsa-Circ-0068530 Expression Changes in Gastric Cancer Cell Line and Human Normal Fibroblast Cell Line

Jentashapir Journal of Cellular and Molecular Biology ◽

10.5812/jjcmb.118967 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Fereshteh Mansoury ◽

Soheila Abdi ◽

Nahid Babaei ◽

Maliheh Entezari ◽

Abbas Doosti ◽

...

Keyword(s):

Gastric Cancer ◽

Magnetic Flux ◽

Cancer Cells ◽

Cell Line ◽

Electromagnetic Fields ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Normal Cells

Background: In recent years, the relationship between cancer cells and electromagnetic radiation has received much attention. Objectives: The present study aimed to evaluate the effects of different intensities of electromagnetic fields on gastric cancer cell lines (AGS). Methods: After preparing AGS and Hu02 (normal) cell lines, they were exposed to magnetic flux densities of 0.25, 0.5, 1, and 2 millitesla (mT) for 18 h. The cell viability was studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of hes1 and hsa-circ-0068530 RNAs were studied by the quantitative Real-time-PCR technique. Results: The inhibition of gastric cancer cell line growth was observed under the influence of electromagnetic fields at different intensities. However, they did not affect the viability of normal cells. A sharp increase in the expression of hes1 and hsa-circ-0068530 genes was observed in normal cells exposed to 2 mT electromagnetic fields. Conclusions: In general, it can be concluded that the effect of electromagnetic fields on gastric cancer cells depends on their intensity. Magnetic flux densities of 0.25 and 0.5 mT had anti-cancer effects and magnetic flux density of 2 mT showed carcinogenic effects.

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The Effect of Dihydroartemisinin on the Malignancy and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190611124644 ◽

2019 ◽

Vol 20 (9) ◽

pp. 719-726 ◽

Cited By ~ 1

Author(s):

Nan Li ◽

Suyun Zhang ◽

Qiong Luo ◽

Fang Yuan ◽

Rui Feng ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Gastric Cancer Cells ◽

Mesenchymal Transition ◽

Expression Levels

Objective: This study aimed to observe the effects of dihydroartemisinin (DHA) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of the human gastric cancer cell line SGC7901 cultured in vitro. Methods: We applied varying concentrations of DHA to SGC7901 cells. Cell proliferation was measured using the cell counting kit-8 (CCK-8). Flow cytometry, Transwell invasion assay, and cell scratch assay were used to investigate the cells’ apoptosis, invasion, and migration. Western blot was used to assess the expression levels of EMT markers E-cadhein and Vimentin, protein kinases Akt and phosphorylated AKT (p-AKT), and the cell transcription factor Snail. Results: DHA can effectively inhibit the malignant proliferation of gastric cancer cells in a time- and dose-dependent manner. In this study, with longer incubation times and increased drug concentrations, the antiproliferation effect of DHA on SGC7901 cells increased gradually (P<0.05). In addition, with the increase of drug concentration, the expression levels of E-cadhein, an epithelial-mesenchymal transition marker, remarkably increased, whereas the protein expression levels of the mesenchymal markers Vimentin, Akt, p-Akt, and Snail significantly decreased (P<0.05). Conclusion: DHA can effectively inhibit the proliferation, invasion, and metastasis of the gastric cancer cell line SGC7901 and induce cancer cell apoptosis. DHA can also downregulate PI3K/AKT and Snail activities and inhibit the epithelial-mesenchymal transition of gastric cancer cells. The potential anticancer effects of DHA deserve further investigation.

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miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45

Cell Biochemistry and Function ◽

10.1002/cbf.2815 ◽

2012 ◽

Vol 30 (5) ◽

pp. 411-418 ◽

Cited By ~ 36

Author(s):

Azadeh Fahim Golestaneh ◽

Amir Atashi ◽

Lida Langroudi ◽

Abbas Shafiee ◽

Nasser Ghaemi ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Cell Line ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Human Gastric Cancer

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CD44-overexpressed gastric cancer imaging by near IR using HA-based supramolecular hydrogels.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.34 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 34-34

Author(s):

Jungmin Park

Keyword(s):

Gastric Cancer ◽

Optical Imaging ◽

Cancer Cells ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Gastric Cancer Cells

34 Background: To establish NIR optical probe based on the HA-based supramolecular hydrogels (HASHs) conjugated with Cy5.5 for CD44-overexpressed gastric cancer imaging. Methods: To establish HASHs, Cy5.5 NHS ester was conjugated with polyethyleneimine (PEI, 25k Da) and mixed with hyaluronic acid (HA, 1M Da) by an electric interaction. The optimazed ideal molar ratio of PEI to HA was confirmed by DLS and gel electrophoresis. The CD44-expression level for various gastric cancer cell lInes (MKN1, MKN28, MKN45, MKN72, AGS, and N87 cells) was evaluated by FACS analysis. For establishment of the gastric cancer xenograft model, CD44-overexpressed gastric cancer cells were implanted into the BALB/c nude mouse's proximal thigh region. For in vitro targeting study, the cellular affinity of HASHs for CD44-low expressed gastric cancer cell line and CD44-overexpressed gastric cancer cell line was verified by confocal microscopy and IHC staing. For in vivo NIR imaging, HASHs were injected into established xenograft mouse via tail vein and NIR optical imaging was conducted time-dependently. Results: The colloidal size of HASHs was 1.4 micrometer and their morphology was confirmed by electron microscopy. CD44-expression level of MKN45 cells was 92.53% that was higher than MKN28 cells (2.66%). After the treatment of HASHs, the endocytosis into the cytosol was examined for MKN45 cells, but not observed in MKN28 cells due to the deficiency of CD44. 30 days after the transplantion of MKN45 cells, for in vivo imaging study, the prepared HASHs were intraveneously injected into tumor-bearing mouse model. By NIR optical imaging, the optical intensity at tumor site was enhanced upto 3 hours and the maximum intensity was 350 times larger than normal tissue. Conclusions: HASHs was established using supramolecular HA and Cy5.5-conjugated PEI for the targeted imaging of CD44-overexpressed gastric cancer cells. In vitro and in vivo studies demonstrated that SHAHs can visualize the individualized CD44-overexpressed gastric cancer cells by non-invasive optical imaging.

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Cisplatin-Resistant Gastric Cancer Cells Promote the Chemoresistance of Cisplatin-Sensitive Cells via the Exosomal RPS3-Mediated PI3K-Akt-Cofilin-1 Signaling Axis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.618899 ◽

2021 ◽

Vol 9 ◽

Author(s):

Meng-Yao Sun ◽

Bo Xu ◽

Qiu-Xue Wu ◽

Wen-Lian Chen ◽

Si Cai ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Mechanism Study ◽

Gastric Cancer Cells ◽

Receptor Cells

Cisplatin is an important agent in first-line chemotherapy against gastric cancer (GC). However, consequential drug resistance limits its effectiveness for the treatment of GC. In this study, a cisplatin resistant gastric cancer cell line SGC7901R was determined by LC-MS/MS with increased exosomal levels of RPS3 protein. SGC7901R cell-derived exosomes were readily taken up by cisplatin-sensitive SGC7901S cells, thus triggering off a phenotype of chemoresistance in the receptor cells. Subsequently, it was demonstrated that exosomal RPS3 was essential for inducing chemoresistance of receptor cells as shown by the acquisition of this phenotype in SGC7901S cells with enforced expression of RPS3. Further mechanism study demonstrated that cisplatin-resistant gastric cancer cell-derived exosomal RPS3 enhanced the chemoresistance of cisplatin-sensitive gastric cancer cells through the PI3K-Akt-cofilin-1 signaling pathway. All these findings demonstrated that cisplatin-resistant gastric cancer cells communicate with sensitive cells through the intercellular delivery of exosomal RPS3 and activation of the PI3K-Akt-cofilin-1 signaling pathway. Targeting exosomal RPS3 protein in cisplatin-resistant gastric cancer cells may thus be a promising strategy to overcome cisplatin resistance in gastric cancer.

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