Li Jieping, Zhou Xiaodong, Lan Xiaopeng, Zeng Guobin, Jiang Xuping, Huang Zongming
Department of Clinic Medical Laboratory, General Hospital of Fujian Corps of CAPF, Fuzhou, 350003, China.
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Tumour Biol. 2016 Mar;37(3):3043-9. doi: 10.1007/s13277-015-4069-8. Epub 2015 Sep 30.
Gastric cancer is one of the leading causes of cancer death worldwide. However, precise molecular mechanisms underlining its development are far from clear. We recently reported that PES1 promoted development of breast cancer and ovarian cancer as an oncogene. In this study, we reported that ablation of endogenous PES1 resulted in significant suppression of cell proliferation and growth and led to cell cycle arrest in G2 or G1 phase, respectively, in two gastric cancer cell lines (AGS and N87) in vitro. Meanwhile, silencing of PES1 obviously decreased expressions of cyclin D1, HIF-1α, and vascular endothelial growth factor (VEGF) expressions and increased p21WAF1 expression. Re-expression of PES1 in these two kinds of PES1 knockdown cells rescued these effects. In vivo, repression of endogenous PES1 expression suppressed gastric tumor growth in nude mice. In addition, 40.7 % (24/59) of gastric cancer tissues showed PES1 expression via immunohistochemical (IHC) staining. However, there were not any positive PES1 stainings in matched adjacent tissues. Our results demonstrated that repression of PES1 changed expressions of some cell proliferation- and angiogenesis-related genes and inhibited gastric cancer growth, and PES1 expression increased in gastric cancer tissues. These results suggest that PES1 may play an important role in development of gastric cancer. PES1 may be a potential target for gastric cancer therapy.
胃癌是全球癌症死亡的主要原因之一。然而，其发生发展的精确分子机制仍远未明确。我们最近报道，PES1作为一种癌基因促进乳腺癌和卵巢癌的发展。在本研究中，我们报道，在体外两种胃癌细胞系（AGS和N87）中，内源性PES1的缺失导致细胞增殖和生长显著受抑，并分别导致细胞周期阻滞于G2期或G1期。同时，PES1的沉默明显降低了细胞周期蛋白D1、低氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的表达，并增加了p21WAF1的表达。在这两种PES1敲低的细胞中重新表达PES1可挽救这些效应。在体内，内源性PES1表达的抑制可抑制裸鼠胃肿瘤的生长。此外，40.7%（24/59）的胃癌组织通过免疫组织化学（IHC）染色显示有PES1表达。然而，在配对的相邻组织中未发现任何阳性的PES1染色。我们的结果表明，PES1的抑制改变了一些与细胞增殖和血管生成相关基因的表达，并抑制了胃癌的生长，且PES1在胃癌组织中的表达增加。这些结果提示，PES1可能在胃癌的发生发展中起重要作用。PES1可能是胃癌治疗的一个潜在靶点。
