临床上胃癌化疗耐药是疗效差的主要原因。最近研究指出，bFGF可能是引起耐药的关键因素。在前期研究中，我们发现bFGF显著上调半乳糖凝集素-1（Gal-1）的表达，且Gal-1在胃癌顺铂耐药细胞中的表达水平显著高于敏感细胞，提示bFGF通过Gal-1介导肿瘤耐药可能是一种新的耐药机制。本课题在此基础上，提出并阐明bFGF通过Gal-1/Ras/NF-κB/PTGS2轴诱导胃癌细胞对顺铂耐药的新机制，并利用我们已获得的具有自主知识产权的bFGF拮抗肽，进一步从细胞和动物水平探讨bFGF拮抗肽逆转bFGF诱导胃癌细胞对顺铂耐药的作用和机制，一方面验证本课题所阐明的bFGF通过Gal-1诱导耐药的分子机制，为肿瘤耐药治疗提供新靶点；另一方面拓展bFGF拮抗肽逆转肿瘤耐药的新功能及其机制研究，为将bFGF拮抗肽研发成一种胃癌化疗耐药的逆转剂奠定基础。

Clinical resistance to chemotherapy of gastric cancer is the main reason for the poor efficacy. Recent researches indicate that bFGF may be a key factor in causing drug resistance, but the exact mechanism is unclear. In previous studies, we found that bFGF can induce resistance of gastric cancer cells to cisplatin, and significantly enhance Galectin-1 expression. Moreover, the expression level of Galectin-1 in cisplatin-resistant gastric cancer cells was significantly higher than that in cisplatin-sensitive ones. These previous data suggest that bFGF mediating resistance to gastric cancer chemotherapy via Galectin-1 may present a new mechanism of drug resistance. On this basis, the hypothesis of a new mechanism of bFGF inducing cisplatin resistance of gastric cancer cells through Gal-1/Ras/NF-κB/PTGS2 axis was proposed and elucidated. Further, the pharmacological effect and mechanism of a novel bFGF antagonist peptide with independent intellectual property, which was previously obtained by phage display screening, reversing bFGF induced cisplatin resistance of gastric cancer cells were investigated at the cell and the animal levels. On one hand, the results will verify the new mechanism of bFGF mediating resistance to gastric cancer chemotherapy via Galectin-1, which was proposed and clarified in this project, and provide new molecular targets for drug resistance therapy. On the other hand, the successful implementation of this project may expand the researches on new function and mechanism of the bFGF antagonist peptide reversing bFGF induced drug resistance, provide a theoretic basis for further developing of bFGF antagonist peptide to reversal agents treating chemotherapy resistance of gastric cancer, and also provide a new strategy to solve the thorny problem of drug resistance in clinic.