| Autor: |
Tsuchida, Takashi, Kijima, Hiroshi, Hori, Sadaaki, Oshika, Yoshiro, Tokunaga, Tetsuji, Kawai, Kenji, Yamazaki, Hitoshi, Ueyama, Yoshito, Scanlon, Kevin J, Tamaoki, Norikazu, Nakamura, Masato |
| Předmět: |
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| Zdroj: |
Cancer Gene Therapy; Mar2000, Vol. 7 Issue 3, p373, 11p |
| Abstrakt: |
Human pancreatic cancer is a lethal malignancy, and the lesions show a very high incidence of point mutations of the K-ras oncogene. These alterations can be used as potential targets for specific ribozyme (Rz)-mediated growth suppression of the cancer cells. We designed an anti-K-ras Rz against mutant K-ras gene transcripts (codon 12, GGT to GTT) and generated a recombinant adenovirus (rAd) to express the Rz (rAd/anti-K-ras Rz). More than 95% of Capan-1 human pancreatic cells were infected with rAd/anti-K-ras Rz when treated with the virus at 200 plaque-forming units/cell. The virus, rAd/anti-K-ras Rz, significantly suppressed mutant K-ras gene expression and inhibited the growth of Capan-1 cells. At 3 days postinfection, we observed maximum growth suppression of the cells, characteristic morphological changes of apoptosis such as nuclear condensation and oligonucleosomal DNA fragmentation, and suppression of bcl-2 oncoprotein. These changes were not found in control virus-infected cells. Our results indicated that the virus rAd/anti-K-ras Rz specifically down-regulated the K-ras/bcl-2 pathway and induced apoptotic changes in Capan-1 pancreatic carcinoma cells. High-efficiency adenovirus-mediated delivery of anti-K-ras Rz could become a significant gene therapy strategy against human pancreatic cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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