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.
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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) |