Increased Thioredoxin-1 Expression Promotes Cancer Progression and Predicts Poor Prognosis in Patients with Gastric Cancer

الملخص EN

Background.

Thioredoxin-1 (Trx-1) is a small redox protein, which plays an important role in many biological processes.

Although increased expression of Trx-1 in various solid tumors has been reported, the prognostic significance and function of Trx-1 in human gastric cancer (GC) are still unclear.

Here, we investigated the clinical and prognostic significance of Trx-1 expression and the function and mechanism of Trx-1 in human GC.

Methods.

We analyzed Trx-1 mRNA expression from the GEO database and Trx-1 protein expression in 144 GC tissues using immunohistochemistry.

Effects of Trx-1 on GC cell were assessed in vitro and in vivo through Trx-1 knockdown or overexpression.

The antitumor effects of the Trx-1 inhibitor, PX-12, on GC cells were investigated.

PTEN and p-AKT expressions were evaluated by Western blotting.

Results.

Increased Trx-1 expression was found in GC tissues and associated with poor prognosis and aggressive clinicopathological characteristics in patients with GC.

High Trx-1 expression predicted poor prognosis, and its expression was an independent prognostic factor for overall survival of GC patients.

Knockdown of Trx-1 expression inhibited GC cell growth, migration, and invasion in vitro and tumor growth and lung metastasis in vivo.

Conversely, overexpression of Trx-1 promoted GC cell growth, migration, and invasion.

We also found that PX-12 inhibited GC cell growth, migration, and invasion.

Overexpression of Trx-1 caused a decrease in PTEN and increase in p-AKT levels whereas silencing Trx-1 caused an increase in PTEN and decrease in p-AKT levels in GC cells.

Inhibition of AKT signaling pathway by MK2206 also inhibited GC cell growth, migration, and invasion.

Conclusion.

Our results indicate that Trx-1 may be a promising prognostic indicator and therapeutic target for GC patients.