RRC ID 56009
著者 Shiromizu S, Kusunose N, Matsunaga N, Koyanagi S, Ohdo S.
タイトル Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice.
ジャーナル J Pharmacol Sci
Abstract Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule.
巻・号 136(4)
ページ 228-233
公開日 2018-4-1
DOI 10.1016/j.jphs.2018.01.008
PII S1347-8613(18)30045-8
PMID 29605274
MeSH Animals Antineoplastic Agents / administration & dosage* Asparaginase / administration & dosage* Asparagine / metabolism Breast Neoplasms / drug therapy* Breast Neoplasms / metabolism Breast Neoplasms / pathology Cell Line, Tumor Disease Models, Animal Drug Administration Schedule Drug Chronotherapy* Female Humans Infusions, Intravenous Mice, Inbred BALB C Neoplasm Transplantation Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
IF 2.575
引用数 4
リソース情報
ヒト・動物細胞 HL-60(RCB3683)