論文 - 詳細
RRC ID | 54014 |
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著者 | Sakagami H, Hara Y, Shi H, Iwama S, Nakagawa M, Suzuki H, Tanaka K, Abe T, Tamura N, Takeshima H, Horie N, Kaneko T, Shiratsuchi H, Kaneko T. |
タイトル | Change in Anticancer Drug Sensitivity During Neuronal Differentiation of PC12 Cells. |
ジャーナル | In Vivo |
Abstract |
BACKGROUND/AIM:Although there are many reports of anticancer drug-induced neurotoxicity, most previous data have been derived from neuronal cell models grown in a variety of culture conditions. This has prevented accurate assessment of the potency of their neurotoxicity and of changes in drug sensitivity of neuronal cells during differentiation. In this study, a simple neuronal differentiation induction system was established and the relative potency of neurotoxicity of eight anticancer drugs was compared during neuronal cell differentiation. MATERIALS AND METHODS:Rat PC12 cells were induced to differentiate into neuronal cells by 50 ng/ml nerve growth factor in serum-free Dulbecco's modified Eagle's medium, followed by overlay of fresh nutrients at day 3, without medium change. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS:During differentiation, PC12 cells became 1.1-to more than 10,000-fold resistant to anticancer drugs. Topoisomerase inhibitors (doxorubicin, SN-38, etoposide) were the most toxic to differentiated PC12 cells, followed by docetaxel, gefitinib, melphalan, 5-fluorouracil and methotrexate. Docetaxel showed the highest cytotoxicity against undifferentiated PC12 cells, but its cytotoxicity was dramatically reduced during differentiation. CONCLUSION:The present study demonstrated considerable variation in the neurotoxicity of anticancer drugs during the cell differentiation process. The present simple assay system may be useful to search for neuroprotective substances. |
巻・号 | 32(4) |
ページ | 765-770 |
公開日 | 2018-1-1 |
DOI | 10.21873/invivo.11306 |
PII | 32/4/765 |
PMID | 29936457 |
PMC | PMC6117783 |
MeSH | Animals Camptothecin / adverse effects Camptothecin / analogs & derivatives Camptothecin / pharmacology Cell Differentiation / drug effects* Doxorubicin / adverse effects Doxorubicin / pharmacology Drug Resistance, Neoplasm / drug effects Drug Screening Assays, Antitumor Etoposide / adverse effects Etoposide / pharmacology Humans Irinotecan Neoplasms / drug therapy* Neoplasms / pathology Neurons / drug effects* PC12 Cells Rats Topoisomerase Inhibitors / adverse effects* Topoisomerase Inhibitors / therapeutic use |
IF | 1.541 |
引用数 | 3 |
リソース情報 | |
ヒト・動物細胞 | PC-12(RCB0009) |