Arsenic trioxide (As₂O₃) inhibits murine WEHI-3 leukemia in BALB/c mice in vivo.
Arsenic trioxide (As₂O₃) is used clinically to treat acute promyelocytic leukemia (APL) and has activity in vitro for induction of apoptosis in several solid tumor cell lines. To investigate the potential therapeutic application of As₂O₃ for leukemia, we analyzed the effects of As₂O₃ on the WEHI-3 cells-induced orthotopic leukemia animal model in vivo in this study. We established the WEHI-3 cells leukemia mice through the injection of murine WEHI-3 cells into BALB/c mice, and they were then treated with As₂O₃ (0.9 and 4.5 mg kg⁻¹ ; p.o.) and/or combined with all-trans-retinoic acid (ATRA), (30 mg kg⁻¹ ; i.p.). The results indicated that (1) As₂O₃ alone or As₂O₃ combined with ATRA promoted the total survival rate of leukemia mice and these effects are dose-dependent; (2) As₂O₃ did not affect the body weight but decreased the spleen weight; however, it did not affect liver weight; (3) As₂O₃ alone or As₂O₃ combined with ATRA increased the levels of CD3 and CD19, indicating that the differentiation of T and B cells were promoted; and (4) As₂O₃ alone or As₂O₃ combined with ATRA did not change the levels of Mac-3 and CD11b markers, indicating that the differentiation of the precursor of macrophage were not inhibited. Based on these observations, As₂O₃ alone or As₂O₃ combined with ATRA have efficacious antileukemia activity in WEHI-3 cells leukemia in vivo.
Lai
Tung-Yuan
TY
School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Lin
Jen-Jyh
JJ
Huang
Wen-Wen
WW
Kuo
Shu-Chu
SC
Wen
Yen-Fang
YF
Lai
I-Cheng
IC
Lin
Chin-Chung
CC
Yang
Jai-Sing
JS
Chung
Jing-Gung
JG
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology
D000943:Antigens, Differentiation; D001152:Arsenicals; D010087:Oxides; C036763:monocyte-macrophage differentiation antigen; D014212:Tretinoin; D000077237:Arsenic Trioxide