Pathology and molecular targeting of human pancreatic cancer

胰腺癌因其扩散迅速、转移频繁以及传统治疗方法的局限性而成为最具致命性的恶性肿瘤之一。因此，开发一种新的胰腺癌治疗策略，如分子靶向治疗，是当前医学最紧迫的问题之一。在这项研究中，我们设计了针对K-ras基因的核酶和针对claudin-1基因的siRNA，并检测了对人胰腺癌细胞的生长抑制作用。我们针对突变的K-ras基因转录产物设计了抗K-ras核酶，并构建了重组腺病毒在细胞中表达。然而，我们尝试了，但未能产生表达NF-kB基因转录子的腺病毒。(2)将抗K-ras核酶基因导入胰腺癌细胞。用腺病毒/抗K-ras核酶感染人胰腺癌细胞。结果2006年(1)转基因核酶在胰腺癌细胞中的应用效果。重组腺病毒/抗K-ras核酶可抑制靶基因的表达，影响胰腺癌组织中细胞凋亡率的增加和血管生成的抑制，从而导致胰腺癌细胞的生长。(2)针对claudin-1基因的siRNA设计。Claudin-1在细胞与细胞间的黏附中发挥作用，并有助于癌症的侵袭。我们设计了针对claudin-1基因转录本的抗claudin-1 siRNA。结果表明，腺病毒载体介导的抗K-ras核酶和/或抗claudin-1 siRNA的高效表达有望成为治疗胰腺癌的一种分子靶向治疗方法。

Human pancreatic cancer is one of the most lethal malignancies because of rapid spread of the tumor, frequent incidence of metastasis and limitations of conventional therapy. Therefore, development of a new therapeutic strategy for pancreatic cancer such as molecular target therapy is one of the most pressing issues in current medicine. In this research projection, we designed ribozymes against K-ras gene and siRNA against claudin-1 gene, and examined growth suppression of human pancreatic cancer cells.RESULTS in 2005(1)Design of ribozymes. We designed anti-K-ras ribozyme against mutant K-ras gene transcripts, and generated a recombinant adenovirus to express the anti-K-ras ribozyme in the cells. However, we tried, but could not generate an adenovirus to express NF-kB gene transcripts.(2)Transfection of anti-K-ras ribozyme into the pancreatic cancer cells. Human pancreatic cancer cells were infected with adenovirus/anti-K-ras ribozyme. The ribozyme suppressed the target K-ras gene expression.RESULTS in 2006(1)Efficacy of the transfected ribozyme in the pancreatic cancer cells. The transfected adenovirus/anti-K-ras ribozyme suppressed the target gene expression, and affected increase of apoptosis and inhibition of angiogenesis in the pancreatic cancer tissue, resulting in growth of the pancreatic cancer cells.(2)Design of siRNA targeting claudin-1 gene. Claudin-1 plays a role in cell-to-cell attachment, and contributes cancer invasion. We designed anti-claudin-1 siRNA targeting claudin-1 gene transcripts. Anti-claudin-1 siRNA suppressed the target gene expression, as well as expression of matrix metalloproteinase-2 which is associated with cancer invasion in the stroma.Our results indicated that high-efficiency adenovirus-mediated delivery of anti-K-ras ribozyme and/or anti-claudin-1 siRNA could become a molecular target therapy against human pancreatic cancer in the future.