Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
Guangzhou Fuda Cancer Hospital & Jinan University, Guangdong, People's Republic of China.
Arch Oral Biol. 2018 Dec;96:74-79. doi: 10.1016/j.archoralbio.2018.08.018. Epub 2018 Aug 30.
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.
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.
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.
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.
评估 T-钙黏蛋白基因在口腔鳞状细胞癌（OSCC）患者中的表达情况，并探讨其对 OSCC 增殖的影响。此外，本研究旨在确定 T-钙黏蛋白的抗增殖作用是否与磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路有关。
采用逆转录定量聚合酶链反应检测 T-钙黏蛋白 mRNA 表达。使用细胞计数试剂盒-8（CCK-8）检测 T-钙黏蛋白对细胞增殖的影响。通过 Kaplan-Meier 法绘制生存曲线，对数秩检验比较亚组间差异。采用 Western blot 检测磷酸化（p）-PI3K、总 PI3K、p-AKT、总 AKT、p-mTOR、总 mTOR 和细胞周期蛋白 D1 的蛋白表达。
结果显示，与正常相邻组织相比，OSCC 组织中 T-钙黏蛋白 mRNA 的表达显著降低（P=0.007），且低 T-钙黏蛋白表达与 OSCC 的临床晚期（P=0.0249）、高病理分级（P=0.0288）和分化不良（P=0.0295）相关。此外，T-钙黏蛋白阴性表达与 OSCC 患者无进展生存期（PFS）较差相关。此外，T-钙黏蛋白的过表达抑制了 OSCC 细胞系的增殖，并抑制了 PI3K/AKT/mTOR 信号通路。重要的是，T-钙黏蛋白与 PI3K 抑制剂 LY294002 联合治疗增强了 T-钙黏蛋白对细胞增殖和 PI3K/AKT/mTOR 通路的抑制作用。
本研究结果表明，T-钙黏蛋白可能通过抑制 PI3K/AKT/mTOR 通路在 OSCC 中发挥肿瘤抑制基因的作用，并且可能是 OSCC 的潜在治疗靶点。
