Cytotoxicity of Simvastatin to Pancreatic Adenocarcinoma Cells Containing Mutant ras Gene
| Autor: | Masayoshi Namiki, Satoshi Tanno, Noriyuki Nishino, Takeshi Obara, Kiyoshi Okamura, Hitoshi Ura |
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| Jazyk: | angličtina |
| Rok vydání: | 1994 |
| Předmět: |
Cancer Research
Simvastatin HMG CoA reductase inhibitor Molecular Sequence Data Protein Prenylation Mevalonic acid Biology Adenocarcinoma Sensitivity and Specificity Article Flow cytometry p21ras Proto-Oncogene Proteins p21(ras) chemistry.chemical_compound Cricetinae medicine Tumor Cells Cultured Animals Humans Point Mutation MTT assay Lovastatin Cytotoxicity Codon medicine.diagnostic_test DNA synthesis Base Sequence Cell Cycle DNA Neoplasm Pancreatic Neoplasms Genes ras Oncology chemistry Cell culture Cancer research Hydroxymethylglutaryl-CoA Reductase Inhibitors Thymidine Pancreatic adenocarcinoma medicine.drug |
| Zdroj: | Japanese Journal of Cancer Research : Gann |
| ISSN: | 1876-4673 0910-5050 |
| Popis: | Simvastatin (SV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits the synthesis of mevalonic acid. The dose-dependent (0.1-100 micrograms/ml) cytotoxicity of SV towards human (MIAPaCa-2, Panc-1, HPC-1, HPC-3, HPC-4, PK-1, PK-9) and hamster (T2) pancreatic carcinoma cell lines was determined by MTT assay. At up to 20 micrograms/ml of SV, the effect was reversible and was restored by 60 micrograms/ml mevalonic acid. Point mutation of Ki-ras at codon 12 in each cell line was detected by means of the modified polymerase chain reaction. The concentration of SV necessary to achieve 50% cytotoxicity was about 10 micrograms/ml, and at this concentration of SV, DNA synthesis assayed in terms of [3H]thymidine uptake, isoprenylation of p21ras examined by Western blotting and cell progression from G1 to S phase of the cell cycle analyzed by flow cytometry were all inhibited. Isoprenylation inhibitors of p21ras, such as SV, are expected to be useful for the treatment of pancreatic cancer. |
| Databáze: | OpenAIRE |
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