Aziz Faisal, Yang Xuesong, Wang Xiaoqi, Yan Qiu
Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, 116044, People's Republic of China.
J Cancer Res Clin Oncol. 2015 Jul;141(7):1221-35. doi: 10.1007/s00432-014-1892-z. Epub 2014 Dec 20.
Helicobacter pylori (H. pylori) is a major causative agent for the induction of chronic gastritis, gastric ulcer and gastric cancer. Celecoxib (COX-2 inhibitor) inhibits gastric cancer cell proliferation, but with low treatment efficacy, limiting its applications. It is important to develop a better strategy to improve the efficacy of celecoxib. Lewis Y (LeY) is a difucosylated oligosaccharide, highly expressed in 60-90% of human epithelial cancers, including gastric cancer. We previously found that H. pylori infection was associated with high level of LeY in gastric cancer.
Herein, we analyzed the correlation between H. pylori and cyclo-oxygenase-2 (COX-2), LeY, gastric markers (CA724 and GRN) in gastric patient's tissue and serum samples by IHC and ELISA. Furthermore, we treated the primary gastric cancer cells with celecoxib, anti-LeY antibody or the combination, and analyzed their therapeutic efficacy on CA724, GRN and COX-2 expression by Western blot, flow cytometry and ELISA.
We found that gastric cancer had significantly high expression of H. pylori, COX-2, CA724, and GRN compared to gastric ulcers and chronic gastritis (P < 0.0001). H. pylori level showed significant correlation with COX-2 (R--0.552), LeY (R--0.861), CA724 (R--0.714) and GRN (R--0.664) (P < 0.0001). Additionally, the combination therapy led to impressive inhibition of gastric cancer cell proliferation, with decreased expression of COX-2, CA724 and GRN through downregulation of MAPKs/COX-2 pathway (P < 0.01).
Our findings suggest that anti-LeY antibody enhances the cancer cell proliferation inhibitory effects of celecoxib, which might be a new feasible way for gastric cancer therapy.
幽门螺杆菌（H. pylori）是诱发慢性胃炎、胃溃疡和胃癌的主要病原体。塞来昔布（COX-2抑制剂）可抑制胃癌细胞增殖，但治疗效果不佳，限制了其应用。开发更好的策略以提高塞来昔布的疗效很重要。Lewis Y（LeY）是一种二岩藻糖基化寡糖，在60%-90%的人类上皮癌（包括胃癌）中高表达。我们之前发现幽门螺杆菌感染与胃癌中LeY的高水平相关。
在此，我们通过免疫组化（IHC）和酶联免疫吸附测定（ELISA）分析了幽门螺杆菌与环氧化酶-2（COX-2）、LeY、胃癌标志物（CA724和GRN）在胃癌患者组织和血清样本中的相关性。此外，我们用塞来昔布、抗LeY抗体或两者联合处理原发性胃癌细胞，并通过蛋白质免疫印迹法、流式细胞术和ELISA分析它们对CA724、GRN和COX-2表达的治疗效果。
我们发现与胃溃疡和慢性胃炎相比，胃癌中幽门螺杆菌、COX-2、CA724和GRN的表达显著更高（P < 0.0001）。幽门螺杆菌水平与COX-2（R = -0.552）、LeY（R = -0.861）、CA724（R = -0.714）和GRN（R = -0.664）呈显著相关（P < 0.0001）。此外，联合治疗导致胃癌细胞增殖受到显著抑制，通过下调丝裂原活化蛋白激酶/COX-2途径使COX-2、CA724和GRN的表达降低（P < 0.01）。
我们的研究结果表明，抗LeY抗体增强了塞来昔布对癌细胞增殖的抑制作用，这可能是胃癌治疗的一种新的可行方法。
