TCF21 inhibits proliferation and chemoresistance through the AKT pathway in human gastric cancer.


Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China. Electronic address: [Email]


In a previous study, we showed that transcription factor 21 (TCF21) is methylated and downregulated in human gastric cancer samples and serves as an independent prognostic factor. However, its biological role and potential mechanism in gastric cancer cells remain unexplored. In the current study, we examined TCF21 expression in 6 gastric cancer cell lines. The BGC-823 and SGC-7901 cell lines were selected for small interfering RNA and plasmid transfection, respectively. The results of the Cell Counting Kit-8 assay demonstrated that TCF21 inhibited gastric cancer cell proliferation. Cell cycle analysis suggested that TCF21 inhibited cell cycle progression in gastric cancer cells. The Matrigel invasion assay demonstrated that TCF21 negatively regulated invasion. The cell adhesion assay showed that TCF21 increased cell adhesion. Gastric cancer cells were treated with cisplatin to explore the role of TCF21 in chemoresistance. Cell Counting Kit-8 assay and AnnexinV/propidium iodide analyses showed that TCF21 overexpression sensitized SGC-7901 cells to cisplatin, whereas its depletion reduced sensitivity in BGC-823 cells. JC-1 staining was performed to measure the effect of TCF21 on mitochondrial potential. TCF21 downregulated mitochondrial membrane potential after treatment with cisplatin. Western blot analysis showed that TCF21 overexpression negatively regulated Bcl-xL, phosphorylated extracellular signal regulated kinase, and phosphorylated AKT expression and induced caspase 3 cleavage. LY294002, an AKT inhibitor, blocked the effect of TCF21 on Bcl-xL, caspase 3 and CDDP-induced apoptosis. Nude mice experiments demonstrated that TCF21 inhibited gastric cancer growth in vivo. In conclusion, our results suggest that TCF21 inhibits gastric cancer growth and chemoresistance possibly through the AKT signaling pathway.


AKT,Chemoresistance,Gastric cancer,Invasion,Proliferation,TCF21,