胃癌是最常见的恶性肿瘤之一，发病率逐年增高。由于临床症状隐匿，多数患者就诊时已发展至中晚期，传统治疗复发率高，预后较差；如何进一步提高疗效、降低死亡率一直是研究的重要课题。随着分子生物学的发展，基因治疗肿瘤已成为研究热点；因此，向肿瘤细胞导入多种相关基因，通过多基因相互协同以提高抗肿瘤效果是基因治疗的发展方向。不同类型的肿瘤对两种自杀基因/前药系统的敏感性不同，推测联合应用CD/5-FC和HSV-TK/GCV可增加抗肿瘤效应。实体瘤的生长、浸润及转移都离不开瘤内新生血管形成，抑制新生血管形成已成为治疗肿瘤的重要靶点之一。血管内皮生长因子(vascular endothelial growth factor, VEGF)是最重要的促血管生成因子之一，在多数肿瘤组织中高表达，与肿瘤的预后及复发密切相关。RNA干扰是在mRNA水平上的基因阻断技术，可高效、特异抑制靶基因表达。本课题通过构建表达融合自杀基因yCDglyTK及VEGF-shRNA的联合基因表达载体，研究其在体内外对胃癌细胞的杀伤效应，以探讨联合应用自杀基因治疗与抗血管生成基因疗法治疗胃癌的可行性。

Gastric cancer (GC) is one of the most common malignancies, the incidence rate has been increasing year by year. Most patients with GC are diagnosed at an advanced stage because of non-specific clinical symptoms. Despite a variety of traditional treatments, the prognosis for patients with advanced GC remains poor, and the recurrence rate is still high. New therapeutic approaches with more efficacy are urgently needed. With the development in molecular biology, gene therapy has been researched extensively. Each suicide gene/prodrug system has is own features, for example, HSV-TK/GCV has a stronger killing effect, while CD/5-FC shows a more powerful “bystander effect”. In addition, cell type dependency might exist with one suicide gene therapy system. Therefore, combination of HSV?TK/GCV and CD/5-FC is expected to have synergistic effects. Angiogenesis plays an essential role in tumor growth, infiltration and metastasis, and inhibition of angiogenesis is a new target for cancer therapy. Vascular endothelial growth factor (VEGF) is a most important pro-angiogenic factor, and is overexpressed in the majority of human cancers. VEGF expression level has a close relationship with prognosis and recurrence rate for cancers. RNA interference (RNAi) technology could inhibit gene expression at mRNA level efficiently and specificly. RNAi could downregulate VEGF expression, resulting in a decreased micro vessel density (MVD) and tumor growth delay in several cancer cell lines, such as nasopharyngeal caner cells, colon cancer cells, and gastric cancer cells. To explore the feasibility of combination gene therapy for gastric cancer using suicide gene and anti-angiogenic gene, a combination gene vector, co-expressing VEGF-shRNA and fusion suicide gene yCDglyTK was constructed in this research, and its inhibiting effect on gastric cancer cells in vivo and in vitro was also studied.

胃癌是最常见的恶性肿瘤之一，发病率逐年增高。由于临床症状隐匿，多数患者就诊时已发展至中晚期，传统治疗复发率高，预后较差；如何进一步提高疗效、降低死亡率一直是研究的重要课题。随着分子生物学的发展，基因治疗肿瘤已成为研究热点；因此，向肿瘤细胞导入多种相关基因，通过多基因相互协同以提高抗肿瘤效果是基因治疗的发展方向。不同类型的肿瘤对两种自杀基因/前药系统的敏感性不同，推测联合应用CD/5-FC和HSV-TK/GCV可增加抗肿瘤效应。实体瘤的生长、浸润及转移都离不开瘤内新生血管形成，抑制新生血管形成已成为治疗肿瘤的重要靶点之一。血管内皮生长因子(vascular endothelial growth factor, VEGF)是最重要的促血管生成因子之一，在多数肿瘤组织中高表达，与肿瘤的预后及复发密切相关。RNA干扰是在mRNA水平上的基因阻断技术，可高效、特异抑制靶基因表达。本课题通过构建表达融合自杀基因yCDglyTK及VEGF-shRNA的联合基因表达载体，研究其在体内外对胃癌细胞的杀伤效应，以探讨联合应用自杀基因治疗与抗血管生成基因疗法治疗胃癌的可行性。