Xu X C, Abuduhadeer X, Zhang W B, Li T, Gao H, Wang Y H
the First Affiliated Hospital of Xinjiang Medical University.
Eur J Histochem. 2013 Nov 18;57(4):e36. doi: 10.4081/ejh.2013.e36.
The receptor for advanced glycation endproducts (RAGE) is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of RAGE in gastric cancer is still elusive. In this study, we investigated the expression and molecular mechanisms of RAGE in gastric cancer cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous tissues (ANCT) were collected, and the expression of RAGE was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, RAGE signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE) used to transfect into human gastric cancer SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase-2 (MMP-2) was detected by Real-time PCR and Western blot assays. Cell proliferative activities and invasive capability were respectively determined by MTT and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. As a consequence, RAGE was found highly expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039), and correlated with lymph node metastases (P=0.026). Knockdown of RAGE reduced cell proliferation and invasion of gastric cancer with decreased expression of AKT, PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.
晚期糖基化终末产物受体（RAGE）是一种致癌性跨膜受体，在多种人类癌症中均有过表达。然而，RAGE在胃癌中的作用仍不明确。在本研究中，我们调查了RAGE在胃癌细胞中的表达及分子机制。收集了40例胃癌及相应的癌旁非癌组织（ANCT），并通过免疫组织化学（IHC）评估活检样本中RAGE的表达。此外，通过构建重组小发夹RNA慢病毒载体（Lv-shRAGE）来阻断RAGE信号，该载体用于转染人胃癌SGC-7901细胞。通过实时定量PCR和蛋白质免疫印迹分析检测AKT、增殖细胞核抗原（PCNA）和基质金属蛋白酶-2（MMP-2）的表达。分别通过MTT和Transwell实验测定细胞增殖活性和侵袭能力。通过流式细胞术分析细胞凋亡和细胞周期分布。结果发现，与ANCT相比，RAGE在癌组织中高表达（70.0%对45.0%，P = 0.039），且与淋巴结转移相关（P = 0.026）。敲低RAGE可降低胃癌细胞的增殖和侵袭能力，同时降低AKT、PCNA和MMP-2的表达，并诱导细胞凋亡和细胞周期停滞。总之，RAGE表达上调与胃癌的淋巴结转移相关，阻断RAGE信号通过AKT途径抑制胃癌细胞的生长和侵袭，这表明RAGE可能是这种侵袭性恶性肿瘤的潜在治疗靶点。
