摘要
Helicobacter pylori （Hp） infection is the major causative agent of gastric cancer, one of the most common malignant tumors in China. However, there is no consensus on the role of Hp infection in gastric cancer. This review summarizes the role of Hp infection in the development of gastric cancer and its potent molecular mechanisms. The immunological drift of helper T lymphocyte mediated specific immune response after Hp infection is a key of carcinogenesis. This process was adjusted by the ratio of INF-γ and IL-4. Nucleotide-binding oligomerization domain 1 and 2 proteins mediate the activation of innate immune response followed by the activation of NF-κB signaling pathways, exhibiting protective effects against Hp infection. Disrupting the dynamic balance between oncogenes and tumor suppressor genes after exposure to Hp infection may promote the transformation of normal epithelial cells into malignant cells. The levels of transforming growth factor （TGF） β1 and epithelial growth factor （EGF） in Hp positive gastric cancer are higher than those in Hp negative gastric cancer. High level of EGF receptor （EGFR） binds to ligand of EGF or TGF and activates tyrosine kinase, thereby promotes tumor cells proliferation. Simultaneously, tumor cells secrete EGF and TGF and stimulate EGFR overexpression, forming a vicious circle. There is also emerging evidence that the two important angiogenic factors, vascular endothelial growth factor and midkine, are correlated with Hp infection. Hp infection was positively correlated with the activation of p-STAT3, thereby up-regulating the levels of Mcl-1, survivin, Bcl-2, Bcl-xL Cyclin D1 and VEGF and other target protein and regulating tumor cells proliferation and apoptosis.
幽门螺杆菌（Helicobacterpylori,Hp）是胃癌的主要致病因素,胃癌是中国最常见的恶性肿瘤之一然而,关于Hp感染在胃癌中的作用尚未达成共识.本综述总结了Hp感染在胃癌发生中的作用及其分子机制.Hp感染后辅助性T淋巴细胞介导的特异性免疫应答漂移是致癌作用的关键,该飘移受INF-γ和IL-4比例影响.寡核苷酸结合区域蛋白1和2可激活先天性免疫应答,进而激活NF-κB信号传导途径,抵制Hp感染.暴露于Hp感染后可破坏癌基因和抑癌基因之间的动态平衡,进而促进正常上皮细胞向恶性细胞的转化.Hp表达阳性的胃癌转化生长因子β1（TGF-β1）和内皮生长因子（EGF）的水平高于Hp表达阴性的胃癌.高水平的EGF受体（EGFR）结合EGF或TGF配体并激活酪氨酸激酶,从而促进肿瘤细胞増殖;同时,肿瘤细胞分泌EGF和TGF并刺激EGFR过度表达,形成恶性循环.也有新的证据表明,两种重要的血管生成因子血管内皮生长因子和中期因子与Hp感染相关.Hp感染可还介导p-STAT3信号通路活化,从而上调Mcl-1,survivin,Bcl-2,Bcl-xL,CyclinD和VEGF等靶蛋白的表达水平,调节肿瘤细胞的増殖和凋亡.
