Background and 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.
Conclusion: 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.