寻找胃癌分子靶点和开发新的胃癌靶向抑制剂对实现胃癌的精准治疗具有重要的临床意义。研究发现H2S能够抑制胃癌细胞的增殖，具有开发成新的抗癌药物的巨大潜力，但其抑瘤机制并不清楚。临床组织病理检测发现潜在的肿瘤治疗靶点hEAG1 K+ 通道也在胃癌中高表达。但是，H2S能否调节hEAG1，尚未见报道。本项目将应用电生理记录技术、分子突变等技术研究H2S对hEAG1的表达和功能影响并寻找它们的相互作用位点，并以胃癌组织和胃癌细胞系为模型，考察H2S合成酶和hEAG1在胃癌组织中的表达是否关联，阐明H2S调节hEAG1的生理学功能，探索H2S功能性调节hEAG1的潜在分子生物学机制。本研究为寻找H2S的潜在抑癌分子靶点、理解H2S的抑癌机制和进一步开发以H2S供体为药物先导物的胃癌治疗打下理论基础。同时对于理解EAG的调控功能和设计以EAG作为新的胃癌治疗靶标提供可能性。

Identifications of the new molecular targets and drugs show the clinical significance for precision treatment of gastric cancer. Evidence of the ability of the gasotransmitter hydrogen sulfide (H2S) and human ether-a-go-go channel (hEAG1) to serve as a regulator of development and progression of gastric cancer, such as, H2S can restrict the proliferation and invasion of gastric cancer which promotes a therapeutic application of H2S donor against gastric cancer, and hEAG1 has been considered as a preferential therapeutic target in hEAG1-expressing cancer types, but the regulatory role of H2S on hEAG1 is unknown. The aims of this study were to investigate the effect of H2S on the current of hEAG1 and identify H2S interaction site(s) by using patch clamp and mutation research, and choose the human gastric cancer tissue and SGC-7901 cells as the models to detect the hEAG1, CBS and CSE proteins in human gastric cancer, analysis the relationship between the expression of those proteins and clinicopathologic features, dissect the impact of physiology process of gastric cancer caused by H2S regulation on hEAG1 and understand the molecular mechanism of hEAG1 regulation by H2S. Our investigation will prove new theoretical ideas and open opportunities for identification of the new H2S molecular target for gastric cancer therapy, understanding the roles of H2S and hEAG1 in gastric cancer, designing H2S donors as the new anti-gastric cancer drugs and turning hEAG1 into true clinically useful gastric cancer target.