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Genetic Profiles Affect the Biological Effects of Serine on Gastric Cancer Cells.

ABSTRACT: A high serine content in body fluid was identified in a portion of patients with gastric cancer, but its biological significance was not clear. Here, we investigated the biological effect of serine on gastric cancer cells. Serine was added into the culture medium of MGC803 and HGC27 cancer cells, and its influence on multiple biological functions, such as cell growth, migration and invasion, and drug resistance was analyzed. We examined the global transcriptomic profiles in these cultured cells with high serine content. Both MGC803 and HGC27 cell lines were originated from male patients, however, their basal gene expression patterns were very different. The finding of cell differentiation-associated genes, ALPI, KRT18, TM4SF1, KRT81, A2M, MT1E, MUC16, BASP1, TUSC3, and PRSS21 in MGC803 cells suggested that this cell line was more poorly differentiated, compared to HGC27 cell line. When the serine concentration was increased to 150mg/ml in medium, the response of these two gastric cancer cell lines was different, particularly on cell growth, cell migration, and invasion and 5-FU resistance. In animal experiment, administration of high concentration of serine promoted cancer cell metastasis to local lymph node. Taken together, we characterized the basal gene expressing profiles of MGC803 and HGC27. The HGC27 cells were more differentiated than MGC803 cells. MGC803 cells were more sensitive to the change of serine content. Our results suggested that the responsiveness of cancer cells to microenvironmental change is associated with their genetic background.

SUBMITTER: Li J

PROVIDER: S-EPMC7411129 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genetic Profiles Affect the Biological Effects of Serine on Gastric Cancer Cells.

Li Jun J Xue Hongzhang H Xiang Zhen Z Song Shuzheng S Yan Ranlin R Ji Jun J Zhu Zhenggang Z Wei Chaochun C Yu Yingyan Y

Frontiers in pharmacology 20200731

A high serine content in body fluid was identified in a portion of patients with gastric cancer, but its biological significance was not clear. Here, we investigated the biological effect of serine on gastric cancer cells. Serine was added into the culture medium of MGC803 and HGC27 cancer cells, and its influence on multiple biological functions, such as cell growth, migration and invasion, and drug resistance was analyzed. We examined the global transcriptomic profiles in these cultured cells ...[more]

PMID: 32848786

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Project description:Background:Proton pump inhibitor (PPI) and other acid-suppressing drugs are widely used in the treatment of gastrointestinal ulcer, upper gastrointestinal bleeding, gastritis, and gastric cancer (GC). About 80% of GC patients receive acid suppression treatment. PPI suppresses the production of gastric acid by inhibiting the function of H+/K+-ATPase in gastric parietal cells and raises the pH value to achieve therapeutic purposes. Some studies have found that PPI had a certain antitumor effect in the proliferation and apoptosis of tumor cells. But the effects of environmental pH on the growth of GC cells and its mechanism are unknown. Therefore, we hoped to find the effects of culture medium pH on the biological behavior of GC cells by in vitro experiments and provide guidance for the use of acid-suppressing drugs in GC patients. Aims:We aimed to observe the effects of pH changes in GC cell culture medium on the cell biological behavior of cancer cells and to analyze the potential mechanisms. We hoped to find out the effect of acid suppression on the growth of GC cells. Methods:The GC cell lines (SGC-7901 and MKN45) were used as the research object. We adjusted the pH value in the cell culture medium to observe the changes in cell viability (MTT), apoptosis (flow cytometry), and invasion (Transwell) at pH?6, pH?7, and pH?8. qRT-PCR and western blot (WB) assays were used to determine the expression changes of genes and proteins (mTOR, AKT, Wnt, Glut, and HIF-1?) at pH?6, pH?7, and pH?8. Results:The results of MTT showed that the viability of SGC-7901 and MKN45 in the pH?8.0 group was significantly weaker than that in the pH?6.0 or pH?7.0 group (P < 0.001). Flow cytometry results showed that the apoptosis of SGC-7901 and MKN45 in the pH?8.0 group was more obvious than that in the pH?6.0 or pH?7.0 group (P < 0.001). Flow cytometry results showed that the apoptosis of SGC-7901 and MKN45 in the pH?8.0 group was more obvious than that in the pH?6.0 or pH?7.0 group (P < 0.001). Flow cytometry results showed that the apoptosis of SGC-7901 and MKN45 in the pH?8.0 group was more obvious than that in the pH?6.0 or pH?7.0 group (?) at pH?6, pH?7, and pH?8. P < 0.001). Flow cytometry results showed that the apoptosis of SGC-7901 and MKN45 in the pH?8.0 group was more obvious than that in the pH?6.0 or pH?7.0 group (. Conclusions:Compared with the microacid environment, the microalkaline environment inhibited the viability, invasion, and expression of genes and proteins (mTOR, AKT, Wnt, Glut, and HIF-1?) but promoted the apoptosis of GC cells and thus inhibited the growth of GC.?) at pH?6, pH?7, and pH?8.

Dataset Information

Genetic Profiles Affect the Biological Effects of Serine on Gastric Cancer Cells.

Publications

Genetic Profiles Affect the Biological Effects of Serine on Gastric Cancer Cells.

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