Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Παρασκευή 31 Αυγούστου 2018

Overexpression of T-cadherin inhibits the proliferation of oral squamous cell carcinoma through the PI3K/AKT/mTOR intracellular signalling pathway

Publication date: Available online 30 August 2018

Source: Archives of Oral Biology

Author(s): Qiuju Wang, Xiaoqin Zhang, Xiaoyu Song, Li Zhang

Abstract
Objective

To evaluate T-cadherin gene expression in patients with oral squamous cell carcinoma(OSCC) and explore its effect on the proliferation of OSCC. Additionally, the present study aimed to determine whether the anti-proliferative effect of T-cadherin was associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway.

Design

A reverse transcription-quantitative polymerase chain reaction was performed to detect T-cadherin mRNA expression. A Cell Counting Kit-8 (CCK-8) assay was used to investigate the effect of T-cadherin on cellular proliferation. The survival curves were plotted by Kaplan-Meier method, and the differences between subgroups were determined by log-rank test. The protein expression of phosphorylated (p)-PI3K, total PI3K, p-AKT, total AKT, p-mTOR, total mTOR and cyclin D1was assessed using western blot.

Results

It was revealed that the expression of T-cadherin mRNA was significantly decreased in OSCC samples compared with normal adjacent ones (P = 0.007), and that low T-cadherin expression was correlated with advanced clinical stage (P = 0.0249), higher pathological grade (P = 0.0288) and poor differentiation (P = 0.0295) of OSCC. In addition, T-cadherin negative expression was revealed to be associated with a worse progression‑free survival (PFS) in patients with OSCC. Furthermore, the overexpression of T-cadherin inhibited the proliferation of OSCC cell lines and suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, the combined treatment of T-cadherin with the PI3K inhibitor LY294002 enhanced the inhibitory effect of T-cadherin on cellular proliferation and the PI3K/AKT/mTOR pathway.

Conclusions

The results of the present study suggested that T-cadherin may function as a tumor suppressor gene in OSCC through suppressing the PI3K/AKT/mTOR pathway, and that it may be a potential therapeutic target for OSCC.



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