Upregulation of TMEFF2 is involved in the antiproliferative effects of vitamin C and tyrphostin AG490 on GES-1 and AGS cells

Transmembrane protein with epidermal growth factor (EGF)-like and two follistatin motifs 2 (TMEFF2) is downregulated in human gastric cancer, and its levels are associated with tumor aggressiveness. Herein, a positive correlation was identified between serum vitamin C levels (µg/ml) and mRNA levels...

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Bibliographic Details
Published in:Oncology letters 2019-01, Vol.17 (1), p.652-659
Main Authors: Han, Hongchao, Xu, Jie, Ji, Weiwei, Wang, Lisheng, Wang, Aikun
Format: Article
Language:English
Subjects:
Antioxidants
Apoptosis
Cancer cells
Cancer therapies
Care and treatment
Cell culture
Cell cycle
Cell growth
Cell proliferation
Gastric cancer
Gene expression
Genetic aspects
Oncology
Penicillin
Proteins
Stomach cancer
Tumor necrosis factor-TNF
Tumorigenesis
Tyrosine
Vitamin C
Vitamin E
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Summary:Transmembrane protein with epidermal growth factor (EGF)-like and two follistatin motifs 2 (TMEFF2) is downregulated in human gastric cancer, and its levels are associated with tumor aggressiveness. Herein, a positive correlation was identified between serum vitamin C levels (µg/ml) and mRNA levels of TMEFF2 in gastric cancer tissue. TMEFF2 silencing promotes cell proliferation in GES-1 normal human gastric epithelial cells and AGS human gastric adenocarcinoma cells. Notably, vitamin C and AG490 exerted antiproliferative effects on the two cell lines. The present study demonstrated that small interfering (si)-RNA-TMEFF2 exerts pro-proliferative effects on GES-1 and AGS cells. The results revealed that vitamin C significantly inhibited the growth of GES-1 and AGS cells by reducing cell viability, decreasing the expression of proliferating cell nuclear antigen (PCNA), and blocking the STAT3 pathway. Moreover, siRNA-TMEFF2-induced enhanced cell viability and PCNA expression were significantly reversed by additional vitamin C treatment; notably, markedly enhanced TMEFF2 expression was observed. Upregulated TMEFF2 expression was observed in association with the antiproliferative effect of AG490. In conclusion, serum vitamin C content (µg/ml) was positively correlated with the mRNA levels of TMEFF2 in gastric cancer tissue. Exploring novel drugs that target TMEFF2 is a potential therapeutic strategy for blocking human GC.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2018.9619