Cytotoxic effect of cyclosporin A alone and in combination with 2-chlorodeoxyadenosine against P388 murine leukemia in vivo.

Background: The purpose of our study was to determine the antileukemic effects of cyclosporin A (CsA) and its interaction with a new purine analogue, 2-chlorodeoxyadenosine (2-CdA, cladribine) on P388 murine leukemia in vivo.

Material/methods: Mice were engrafted intraperitoneally (i.p.) with 106 P388 leukemia cells on day 0 of each step of the two-step experiment. All treatments were initiated on the next day (day 1) as daily i.p. injections and lasted for five consecutive days. In the first part of the experiment, designed to establish the antileukemic effect of CsA, the mice received 10, 15, 20, 25 or 30 mg/kg of CsA. In the second part, where the interaction between CsA and 2-CdA was examined, the animals were administered CsA at a dose of 15 mg/kg, or 2-CdA at a dose of 20 mg/kg, or CsA combined with 2-CdA at the same doses as in monotherapy.

Results: CsA did not influence the survival time of mice with P388 leukemia at any dose. CsA was used for the interaction study at a dosage of 15 mg/kg, as this was best tolerated by the animals. The mice treated with combination therapy using CsA and 2-CdA survived longer than those treated with 2-CdA monotherapy (p=0.00015).

Conclusions: Our study revealed that CsA alone does not increase the survival time of mice with P388 leukemia, but it augments the antileukemic effect of 2CdA.