Anti-K-ras ribozyme induces growth inhibition and increased chemosensitivity in human colon cancer cells.
Colon cancer is one of the carcinomas that is resistant to a variety of therapies. To develop a new therapy by regulating the activated K-ras gene in colon cancers, we prepared synthetic DNA encoding the ribozyme (catalytic RNA), and inserted it into an expression vector (LNCX) originated from a retrovirus. Transfection of the vector into SW620 human colon cancer cells brought about significant suppression of K-ras mRNA synthesis and inhibition of the cell growth. Studies in athymic mice, in which K-ras ribozyme-introduced SW620 cells were transplanted, also revealed a marked reduction of tumor growth in vivo. Furthermore, the ribozyme-introduced tumors became more sensitive to treatment with anti-cancer drugs such as cisplatin, adriamycin, 5-fluorouracil, vincristine, and etoposide. These data suggest that the possible efficacy of anti-K-ras ribozyme increases the chemosensitivity of human colon cancers as well as the inhibitory effect on the growth of human colon cancers.
Funato
T
T
Department of Molecular Diagnostics, Tohoku University School of Medicine, Sendai, Japan.
Ishii
T
T
Kambe
M
M
Scanlon
K J
KJ
Sasaki
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D018274:Electroporation; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006131:Growth Inhibitors / Q000235:genetics* / Q000494:pharmacology*; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics / Q000494:pharmacology*; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D016337:RNA, Catalytic; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)