Yang Xiangming, Jing Da, Liu Lijun, Shen Zhiyuan, Ju Jun, Ma Chao, Sun Moyi
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
Oncol Rep. 2015 Apr;33(4):1650-6. doi: 10.3892/or.2015.3750. Epub 2015 Jan 26.
Salivary adenoid cystic carcinoma (SACC) is a malignant tumor that is characterized by perineural invasion (PNI). p53 is an essential tumor-suppressor gene and p53 mutations play a critical role in tumor occurrence and progression (e.g., pancreatic, prostate and head and neck cancer). However, the regulatory role of the p53 gene in SACC and the PNI process remains unknown. In the present study, we employed RNA interference technique to downregulate p53 gene expression in SACC-83 cells to explore the role of p53 in the PNI process. Our results showed that the downregulation of the p53 gene induced significant 'epithelial-mesenchymal transition (EMT)-like changes' in SACC-83 cells, including decreased expression levels of epithelial markers (E-cadherin, EMA and CK5) and increased expression levels of mesenchymal markers (vimentin, N-cadherin and C-cadherin). The downregulation of p53 also caused a lower apoptotic index of Annexin V-FITC/PI and a lower number of SACC-83 cells in the second G0/G1 phase of the cell cycle. Furthermore, the downregulation of the p53 gene resulted in a significant increase in PNI activity in the SACC-83 cells. Thus, our findings revealed that downregulation of p53 promoted in vitro PNI activity through 'EMT-like changes' in SACC-83 cells. The present study suggests the essential regulatory role of p53 in the PNI activity of SACC cells, and implies that p53 may be a new target gene for the clinical treatment of SACC.
涎腺腺样囊性癌（SACC）是一种以神经周侵犯（PNI）为特征的恶性肿瘤。p53是一种重要的肿瘤抑制基因，p53突变在肿瘤发生和进展（如胰腺癌、前列腺癌和头颈癌）中起关键作用。然而，p53基因在SACC及PNI过程中的调控作用尚不清楚。在本研究中，我们采用RNA干扰技术下调SACC - 83细胞中p53基因的表达，以探讨p53在PNI过程中的作用。我们的结果表明，p53基因的下调在SACC - 83细胞中诱导了显著的“上皮 - 间质转化（EMT）样变化”，包括上皮标志物（E - 钙黏蛋白、EMA和CK5）表达水平降低，以及间质标志物（波形蛋白、N - 钙黏蛋白和C - 钙黏蛋白）表达水平升高。p53的下调还导致Annexin V - FITC/PI凋亡指数降低，以及处于细胞周期第二个G0/G1期的SACC - 83细胞数量减少。此外，p53基因的下调导致SACC - 83细胞中PNI活性显著增加。因此，我们的研究结果表明，p53的下调通过SACC - 83细胞中的“EMT样变化”促进了体外PNI活性。本研究提示p53在SACC细胞的PNI活性中具有重要的调控作用，并暗示p53可能是SACC临床治疗的一个新的靶基因。
