Tumor Specific Gene Therapy for Pancreatic Cancer

本研究的目的是评估N116Y是否可以抑制携带K-ras突变的胰腺癌细胞系的增殖并导致恶性表型的逆转。通过筛选培养基上的菌落形成效率来评价N116Y的生长抑制活性。为了研究N116Y对肿瘤表型的影响，我们建立了表达N116Y的克隆，并分析了其在软琼脂中的生长能力和裸鼠的致瘤性。转染pZIP-N116Y后，8株胰腺癌细胞株的生长均受到强烈抑制。此外，表达n116y的无性系扩散程度降低，失去了不依赖锚定的生长能力。此外，它们在体内无致瘤性。N116Y显著抑制胰腺癌细胞系的生长并导致恶性表型的逆转。这些结果提示N1I6Y可能是用于胰腺癌基因治疗的候选基因。

The aim of this study is to assess whether N116Y can inhibit the proliferation of pancreatic cancer cell lines carrying K-ras mutations and cause reversion of the malignant phenotype. The growth inhibition activity of N116Y was evaluated by the colonyforming efficiency in selection medium. In order to examine the effect of N116Y on the neoplastic phenotype, we established N116Y-expressing clones and analyzed their growth ability in soft agar and tumorigenicity in nude mice. The growth of the eight pancreatic cancer cell lines was strongly inhibited by the transfection of pZIP-N116Y.Moreover, the N116Y-expressing clones became less spread and lost their anchorage-independent growth ability. Furthermore, they were nontumorigenic in vivo. N116Y significantly inhibits the growth of pancreatic cancer cell lines and causes reversion of the malignant phenotypes. These results suggest that N1I6Y may be a candidate gene for use in the gene therapy of pancreatic cancer.