Induction of resistance to etoposide and adriamycin in a human glioma cell line treated with antisense oligodeoxynucleotide complementary to the messenger ribonucleic acid of deoxyribonucleic acid topoisomerase II alpha
Autor: | Mitsuo KURIYAMA, Kimiko TSUTSUI, Ken TSUTSUI, Yasuhiro ONO, Takashi TAMIYA, Kengo MATSUMOTO, Tomohisa FURUTA, Takashi OHMOTO |
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Rok vydání: | 1997 |
Předmět: |
Gene isoform
DNA Complementary Cell Survival Alpha (ethology) Gene Expression Regulation Enzymologic chemistry.chemical_compound Antigens Neoplasm Glioma medicine Tumor Cells Cultured Humans Topoisomerase II Inhibitors RNA Messenger Etoposide Cell Line Transformed Antibiotics Antineoplastic biology Dose-Response Relationship Drug business.industry Brain Neoplasms Topoisomerase Oligonucleotides Antisense medicine.disease Molecular biology Antineoplastic Agents Phytogenic Drug Resistance Multiple Multiple drug resistance DNA-Binding Proteins Isoenzymes DNA Topoisomerases Type II chemistry Cell culture Doxorubicin Drug Resistance Neoplasm biology.protein Surgery Neurology (clinical) business DNA Cell Division medicine.drug |
Zdroj: | Neurologia medico-chirurgica. 37(9) |
ISSN: | 0470-8105 |
Popis: | Acquisition of resistance to anticancer agents is a serious problem for cancer chemotherapy. The present study analyzed the relationship between expression of the alpha isoform of deoxyribonucleic acid (DNA) topoisomerase II (topo II alpha) and chemosensitivity to topo II inhibitors by modulating the level of topo II alpha expression. A phosphorothioate analogue of an 18-nucleotide oligomer which is complementary to the translation initiation site of the human topo II alpha messenger ribonucleic acid sequence was used to suppress the expression of topo II alpha in a human glioma cell line (U373MG). The topo II alpha activity of the treated cells was reduced to 1/3 of untreated cells in a decatenation assay using kinetoplast DNA. Antisense oligoDNA-treated cells showed mild resistance to the topo II inhibitors, etoposide and adriamycin, of about 2.0 fold and 1.5 fold, respectively, compared to control cells. Only partial reduction in the activity of topo II alpha in the glioma cell line can cause a measurable resistance to topo II inhibitors, implying that the degree of topo II expression is correlated with chemosensitivity to topo II inhibitors. |
Databáze: | OpenAIRE |
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