| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2009-01-18 |
| タイトル |
|
|
タイトル |
培養悪性腫瘍細胞株を用いたMDR1阻害剤による抗腫瘍薬治療増強効果と99mTc-MIBIによる薬剤耐性の評価 |
|
言語 |
ja |
| タイトル |
|
|
タイトル |
Study on potentiation of antitumor agent by MDR1 inhibitors in malignant tumor cells: Monitoring multidrug resistance using 99mTc-MIBI and comparison with expression of MDR1 mRNA |
|
言語 |
en |
| 言語 |
|
|
言語 |
jpn |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
VCR-resistant malignant tumors |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
MDR1 inhibitors |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
99mTc-MIEI |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
MDR1 mRNA expression |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 作成者 |
内藤, 雄一郎
笹嶋, 寿郎
佐藤, 知
溝井, 和夫
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
The aim of this study was to explore whether 99mTc-methoxyisobutylisonitrile (MIBn is suitable for elucidation of multidrug resistance and prediction of potentiation of antitumor agents by MDRI inhibitors in malignant tumor cells. Tumor cells (RG2 and C6 gliomas, Walker 256 mammary carcinoma) were continuously incubated with low dose vincristine to induce and maintain multidrug resistance. MTT assays demonstrated significant increases of surviving fractions in all vincristne (VCR) -resistant sublines as compared with those of drug-naive cell lines. Double-label accumulation studies (99mTc-MIBI, 14C-TdR) were performed in all drug-naive cell lines and VCR-resistant sublines. In all VCR-resistant sublines, RT-PCR revealed higher expression of MDRI mRNA as compared with drug-naive cell lines. 99mTc-MIBI accumulation in VCR-resistant sublines expressing higher levels of MDRI mRNA was significantly lower than in drug-naive cell lines expressing lower levels of MDRI mRNA. However, there were no significant differences in cell proliferation as measured by 14CTdR accumulation rate. 99mTc-MIBI accumulation is negatively correlated with MDRI mRNA levels among drug-naive cell lines and VCR-resistant sublines. These findings indicated that the development of drug resistance was associated with enhanced 99mTcMIBI extrusion. After pretreatment with MDRI inhibitors (verapamil, cyclosporin A, FK506), surviving fractions of all VCR-resistant sublines significantly decreased as compared with those of non-treated VCR-resistant sublines. MTT assays revealed enhanced effects on VCR cytotoxity following pretreatment with MDRI inhibitors. ggmTc-MIBI accumulation significantly increased after one-hour pretreatment with MDRI inhibitors in all VCR-resistant sublines. In contrast, there were no significant differences in MDRI mRNA levels between non-treated and MDRI inhibitor-treated VCR-resistant sublines. MDRI inhibitors had no significant effects on cell proliferation as measured by 14C-TdR accumulation rate. These findings indicated that MIBI-dependent mechanisms allowing VCR extrusion were functionally inhibited by MDRI inhibitors. ggmTc-MIBI may be a suitable imaging agent for detecting MDRI-mediated drug resistance and for monitoring therapeutic effects of MDRI inhibitors in malignant tumors. ggmTc-MIBI SPECT is expected to provide more definitive criteria for monitoring multidrug resistance and for predicting potentiation of antitumor agents by MDRI inhibitors in patients with malignant brain tumors. |
|
言語 |
en |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 書誌情報 |
秋田医学
巻 31,
号 1,
p. 11-21,
発行日 2004-05-01
|
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
03866106 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AN00009294 |
| 出版者 |
|
|
出版者 |
秋田医学会 |
akigaku31-1b.pdf (669.6 kB)
