A nuclease-resistant protein kinase C alpha ribozyme blocks glioma cell growth.
We investigated the cleavage activity, stability, and efficacy of 2'-amino pyrimidine modified ribozymes on malignant glioma growth. A synthetic protein kinase C alpha (PKC alpha) ribozyme with complete pyrimidine nucleotide substitution retained a comparable cleavage activity compared with the unmodified ribozyme. The half-life of the modified ribozyme in serum was increased 14,000-fold compared with the unmodified version. The PKC alpha modified ribozyme inhibited glioma cell growth in vitro as a result of the inhibition of PKC alpha gene expression. A single injection of cationic liposome ribozyme complexes into glioma tumors inhibited tumor growth, demonstrating both the efficacy of the ribozyme and a major role of PKC alpha in tumor growth.
Sioud
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Department of Immunology, Norwegian Radium Hospital, Montebello, Oslo, Norway. mosioud@embnet.uio.no
Sørensen
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000235:genetics; D004720:Endonucleases / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D051571:Protein Kinase C-alpha; D016337:RNA, Catalytic / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007527:Isoenzymes; D016337:RNA, Catalytic; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D004720:Endonucleases