Effects of arsenic trioxide under different administration ways on T-cell lymphoma xenografts in nude mice: in vivo and in vitro experiments.
OBJECTIVE
In vitro, arsenic trioxide (As(2)O(3)) can inhibit proliferation of many lymphoma cell lines. In clinic, it also can be used to treat many subtypes of lymphoma. But the dosage and administration ways are undetermined yet. In this research, we studied the antitumor effect of As(2)O(3) with different administration ways on T-cell lymphoma and observed the toxicity.


METHODS
Murine T-cell lymphoma cell line EL4 was treated with As(2)O(3) of eight concentrations. Cell proliferation was detected by MTT assay. Cell apoptosis was evaluated by flow cytometry with Annexin-V-FITC/PI staining and observed under electroscope and fluorescent microscope. EL4 cells were inoculated into nude mice to establish lymphoma models. The effect of As(2)O(3) on lymphoma in nude mice was observed.


RESULTS
As(2)O(3) inhibited the proliferation of EL4 cells with a 50% inhibition concentration (IC(50)) of 1.28 micromol/L at 72 h (p < 0.05). When treated with the same total dose of As(2)O(3) by 4 mg(kg d)(-1) for seven days or 2 mg(kg d)(-1) for 14 days, the inhibition rates of tumor growth in mice were equivalent (58.8% vs. 55.6%, p = 0.351). Apoptotic cells were increased and apoptotic bodies were observed in xenograft tumor tissues. Acute liver damage is the major toxicity.


CONCLUSIONS
Shortening the administration course and increasing the daily dosage of As(2)O(3) can be considered as a reasonable model for treating advanced/refractory lymphomas.
Gao
Yan
Y
State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Cai
Qing-Qing
QQ
Li
Su
S
Bu
Qing
Q
Liao
Hong
H
Zhou
Yin
Y
Huang
Hui-Qiang
HQ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D020128:Inhibitory Concentration 50; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide