Helicobacter pylori promotes gastric epithelial cell survival through the PLK1/PI3K/Akt pathway.
Helicobacter pylori promotes gastric epithelial cell survival through the PLK1/PI3K/Akt pathway.
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幽门螺杆菌通过PLK1/PI3K/Akt途径促进胃上皮细胞存活
DOI：
10.2147/ott.s164749
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发表时间：
2018
影响因子：
4
通讯作者：
Lu N
中科院分区：
文献类型：
--
作者：
Xu W;Huang Y;Yang Z;Hu Y;Shu X;Xie C;He C;Zhu Y;Lu N
目的幽门螺杆菌（Helicobacter pylori，H. pylori）感染在胃癌发生过程中起着重要作用。但其复杂的致病机制尚不清楚。Polo样激酶1（PLK 1）参与多种人类恶性肿瘤的发生，包括胃癌。因此，本研究旨在阐明PLK 1在H.幽门螺杆菌诱导的胃癌发生及其信号转导机制。材料与方法检测了166例胃癌患者胃癌发生发展过程中不同阶段PLK 1的表达，并建立了蒙古沙土鼠H. pylori感染。采用Cell Counting Kit-8检测胃癌细胞的存活率。结果PLK 1在胃癌组织中的表达明显高于癌旁组织。PLK 1在肠上皮化生、异型增生和胃癌组织中的表达高于慢性非萎缩性胃炎组织。值得注意的是，PLK 1在H. pylori阴性的组织中，H.肠化生期幽门阳性组织。此外，H. pylori感染可使蒙古沙土鼠胃粘膜上皮细胞PLK 1表达增加，且与幽门螺杆菌感染时间呈正相关。幽门感染抑制PLK 1可显著降低H. pylori诱导的细胞增殖。此外，MKN-28细胞与H. pylori导致PLK 1、p-PTEN和下游PI 3 K/Akt通路显著增加，用PLK 1抑制剂预处理逆转了这些分子变化。结论PLK 1参与了H. pylori通过激活PI 3 K/Akt信号通路在早期诱导胃癌发生。这些结果可能有助于开发新的控制策略，H。幽门螺杆菌感染相关的胃癌。
Purpose Helicobacter pylori (H. pylori) infection plays a critical role in the process of gastric carcinogenesis. However, the complicated pathogenic mechanism is still unclear. Polo-like kinase 1 (PLK1) is involved in the development of multiple human malignancies, including gastric cancer. Therefore, this study aimed to elucidate the role of PLK1 in H. pylori-induced gastric carcinogenesis and the underlying signaling mechanism. Materials and methods We detected the expression of PLK1 in 166 patients in different stages of gastric carcinogenesis as well as the established Mongolian gerbil model with H. pylori infection by immunohistochemistry. Cell Counting Kit-8 was used to estimate the survival of gastric cancer cells. Results We found that PLK1 expression in gastric cancer tissues was significantly higher than that of paired adjacent mucosa. PLK1 expression was increased in intestinal metaplasia, dysplasia, and gastric cancer tissues compared to chronic non-atrophic gastritis tissues. Notably, PLK1 expression was much lower in H. pylori-negative tissues than in H. pylori-positive tissues at intestinal metaplasia stage. In addition, H. pylori infection increased PLK1 expression in the gastric epithelial cells of the Mongolian gerbil model, which was positively related to the duration of H. pylori infection. Inhibition of PLK1 significantly reduced H. pylori-induced cell proliferation. Furthermore, incubation of MKN-28 cells with H. pylori resulted in a significant increase in PLK1, p-PTEN, and the downstream PI3K/Akt pathway, and pretreatment with a PLK1 inhibitor reversed these molecular changes. Conclusion PLK1 is involved in H. pylori-induced gastric carcinogenesis at the early stage by activating the PI3K/Akt signaling pathway. These results may contribute to the development of new control strategies for H. pylori infection-related gastric cancer.