RBMS3上调SFRP1阻断Wnt通路抑制胃癌增殖的机制研究

The prognosis of gastric cancer with an unclear mechanism is poor. The role of RBMS3 in tumor is of growing importance. Our previous study has found that the expression of RBMS3 in 191 cases with gastric cancer was lower than that in 46 normal gastric samples with immunohistochemistry chip. The five-year follow-up data showed that the survival was shorter in patients with a negative expression of RBMS3 than that with a positive one. It means that the RBMS3 may play an important role in gastric cancer. Our further study has shown that the proliferation of gastric cancer line AGS could be inhibited by the expression of RBMS3 with the upregulation of the tumor suppress gene SFRP1, and blocking the Wnt pathway and down-regulation the protein expression of β-catenin and c-myc. We hypothesize that the RBMS3 may suppress the proliferation of gastric cancer with an upregulation of the expression of SFRP1 and blocking the Wnt pathway. Based on our previous research, the relationship between RBMS3 and gastric cancer from a large sample would be retrospectively investigated in this study, to clarify the suppression of the tumor cell proliferation by the over expression of RBMS3 with gastric cancer lines, and to explore the mechanism with western blotting and protein-protein interacting technology. The purpose of the study is to find out a new treatment target for gastric cancer.

胃癌预后差且发病机制不明，RBMS3在肿瘤中的作用正日益受到重视。我们前期工作发现191例胃癌及46例正常胃组织芯片免疫组化染色显示RBMS3在胃癌中低表达，5年以上临床随访资料证实RBMS3阴性患者比RBMS3阳性患者生存期显著缩短，提示RBMS3在胃癌发生发展中发挥着重要作用；进一步研究发现在胃癌细胞株AGS中过表达RBMS3显著抑制肿瘤细胞的增殖，同时伴随SFRP1的表达上调，以及SFRP1阻断的Wnt通路下游蛋白β-catenin和c-myc的下调，我们提出RBMS3可能通过上调SFRP1阻断Wnt通路抑制胃癌细胞增殖的假设。本项目拟在前期实验基础上，大样本回顾分析研究RBMS3与胃癌的临床相关性，明确在多个胃癌细胞系中过表达RBMS3抑制肿瘤细胞增殖的作用，并应用免疫印迹和蛋白互作等技术阐明其作用机制,以期为胃癌的治疗提供新的靶点。

胃癌预后差且发病机制不明。RBMS3可能在胃癌发生发展中起重要作用，但目前国内外未见RBMS3在胃癌研究中的报道。本项目从大样本回顾分析中研究RBMS3与胃癌的临床相关性，通过胃组织芯片免疫组化染色结果发现RBMS3在胃癌中低表达，且SFRP1在胃癌组织中也低表达；RBMS3与SFRP1的表达具有正相关关系；低RBMS3表达与肿瘤低分化明显相关。结合5年以上临床随访资料证实了RBMS3阴性患者比RBMS3阳性患者生存期显著缩短，多因素分析表明RBMS3的表达水平是胃癌患者的独立预后因子。体外细胞实验结果表明，在多个胃癌细胞系中过表达RBMS3可抑制肿瘤细胞增殖的作用，本项目研究发现，RBMS3是胃癌患者预后的独立预测因子，其表达水平与胃癌患者预后紧密相关，未来可作为胃癌的早期检测指标或开发成胃癌免疫治疗的精准靶标。