胃癌居我国恶性肿瘤死亡率第三位。单一治疗方法效果局限，申请人前期发表成果显示：1）基于“胃癌脾虚”病机形成的健脾为主中药复方胃肠安，在改善胃癌患者脾虚证并延长生存期方面具有确切临床疗效；2）胃肠安有抑制胃癌细胞增殖、诱导凋亡作用；3）可下调PTBP3的表达，并通过PTBP3相关选择性剪接调控多个基因表达发挥抑瘤作用。在此基础上发现：Id1经选择性剪接产生促增殖侵袭的异构体Id1a和抑制增殖的Id1b，而Id1的转录后调控可能与PTBP3选择性剪接相关。据此，提出假说：胃肠安通过选择性剪接调控Id1不同异构体表达是其抑制胃癌进展的机制之一。本项目拟通过RNA干扰、定点突变、蛋白质-核酸紫外交联等分子生物学技术，研究选择性剪接对Id1a和Id1b表达的调控机制，及PTBP3在其中的作用，阐明胃肠安通过调控Id1异构体表达变化抑制胃癌细胞恶性进展的分子机制，丰富和发展“胃癌脾虚”理论的科学内涵。

Gastric cancer ranks the third by the incidence of mortality in China. Any single treatment now was limited in efficacy. Previous researches showed: 1) Based on the pathogenesis “Spleen-deficiency-caused gastric cancer”, the Spleen Qi inspiration compound “Wei Chang An” has the exact clinical effect on eliminating the Spleen-deficiency symptoms and reducing the recurrence and metastasis and prolonging the survival time of advanced gastric cancer. 2) “Wei Chang An” could inhibit the gastric cancer cell proliferation and induce apoptosis. 3) “Wei Chang An” could down-regulated the expression of PTBP3, and inhibit the gastric cancer cell through PTBP3 related alternative splicing to regulate multiple gene’s expression. Furthermore, we found DNA binding inhibitor Id1 produced different isoforms of Id1a (promoting proliferation and invasion) and Id1b (inhibiting proliferation) by alternative splicing and played a major role in promoting malignant progression of gastric cancer cells, and the post-transcriptional control of Id1 might be related to alternative splicing of PTBP3. Based on the above, we put forward the hypothesis: “Wei Chang An” down-regulated of Id1 isoforms by alternative splicing is one of the mechanisms of progress in inhibition of gastric cancer. To prove the hypothesis, in this study we use RNA interference, site directed mutagenesis, protein nucleic acid ultraviolet cross-linking and other molecular biological techniques to study the regulatory mechanism of alternative splicing on the expression of Id1a and Id1b, and the relationship in which the PTBP3 had, so as to elucidate the molecular mechanism of “Wei Chang An” inhibiting the of malignant progression of gastric cancer cells through PTBP3 related alternative splicing Id1 isoforms, as well as to prove the scientific connotation of the theory of “Spleen-deficiency-caused gastric cancer”.