TFF1 inhibits proliferation and induces apoptosis of gastric cancer cells in vitro

Abstract

Trefoil Factor Family (TFF) plays an essential role in the intestinal epithelial restitution, but the relationship between TFF1 and gastric cancer (GC) is still unclear. The present study aimed to determine the role of TFF1 in repairing gastric mucosa and in the pathogenesis of GC. The TFF1 expression in different gastric mucosas was measured with immunohistochemistry. Then, siRNA targeting TFF1 or plasmids expressing TFF1 gene were transfected into BGC823 cells, SGC7901 cells and GES-1 cells. The cell proliferation was detected with MTT assay and apoptosis and cell cycle measured by flow cytometry. From normal gastric mucosa to mucosa with dysplasia and to gastric cancer, the TFF1 expression had a decreasing trend. Down-regulation of TFF1 expression significantly reduced the apoptosis of three cell lines and markedly facilitated their proliferation but had no significant effect on cell cycle. Over-expression of TFF1 could promote apoptosis of three cell lines and inhibit proliferation but had no pronounced effect on cell cycle. TFF1 can inhibit proliferation and induce apoptosis of GC cells in vitro.

TFF1 activates p53 through down-regulation of miR-504 in gastric cancer

“…In a mouse model, loss of TFF1 promotes gastric dysplasia and adenocarcinoma [3, 8, 9]. Previous studies have shown that TFF1 inhibits growth and promotes apoptosis in gastric cancer cells [11, 12]. However, the mechanism by which TFF1 exerts these effects is still unclear.…”

“…Using a Tff1 knockout mouse model, we and others have provided evidence supporting the tumor suppressor function of TFF1 and its anti-inflammatory role in gastric cancer [3, 8, 9]. While there are evidences showing that TFF1 suppresses growth and induces apoptosis in gastric cancer cells [10-12], one study has shown that recombinant TFF1 could have anti-proliferative and anti-apoptotic effects in gastrointestinal cells [13]. The mechanisms by which TFF1 might exert its tumor suppressor functions and promote cell death remain largely unrecognized.…”

Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer

“…From normal gastric to dysplasia and to gastric carcinoma mucosa, the TFF1 expression has a decreasing trend [28]. All normal gastric tissues expressed TFF1, but 53.8% [24]/ 58.3% [72]/ 67.50% [76]/ over 70% [77] of GCs showed reduced TFF1 expression.…”

A functional polymorphism in TFF1 promoter is associated with the risk and prognosis of gastric cancer

“…Genes that could modulate cell growth and death have the potential to be the chemosensitizer of 5‐FU . TFF1 was reported having the function in cell growth and death . And in our functional studies, overexpression of TFF1 in gastric cancer cells enhanced the cytotoxicity of 5‐FU by inhibiting proliferation and promoting apoptosis.…”

“…43,44 TFF1 was reported having the function in cell growth and death. [45][46][47] And in our functional studies, overexpression of TFF1 in gastric cancer cells enhanced the cytotoxicity of 5-FU by inhibiting proliferation and promoting apoptosis. NF-jB is the key regulatory signaling molecule responding to multiple stress stimuli, 48 which can be activated by 5-FU and thereby induce the chemoresistance 30,49 through altering the expression of apoptosis-related proteins (such as Bcl-2, Bcl-xl) 50 and cellcycle regulators (such as c-MYC and cyclin D1).…”