The Effects of Berbamine in Nude Mice Xenograft Model of Human Leukemic Cells.

Background: Berbamine is a kind of bis-benzylisoquinoline extracted from Chinese herb. In our past research, it had been proven that berbamine could obviously inhibit the proliferation and induce apoptosis in different kinds of leukemic cell lines including K562, Jurkat, NB4 in a time-and dosage-dependent manner in vitro. The down-regulation expressions of survivin gene, bcr/abl gene and bcr/abl -related P²¹⁰ may play an important role in the apoptotic effect of Berbamine in leukemic cells. However, the effects in vivo and its mechanism remain to be identified. In this study, the effects of berbamine in nude mice bearing human leukemic cell xenografts were tested.

Methods: The nude mice (BALB/C-nu/nu) were pre-treated with X ray 400cGy/2min, then 2×10⁷ K562 cells and Jurkat cells were subcutaneously injected into the mice respectively. Rapid growth of solid tumors was observed in nude mice. One week later, the tumor-bearing mice were randomly divided into three treatment groups: untreated controls; berbamine-treated group (a dose of 1.0mg/day × 20 day, subcutaneously injected); Ara-C-treated group(a dose of 0.8mg/day, × 7 day, subcutaneously injected). Four weeks later, all the experimental mice were euthanized.

Results: Mice that received berbamine had significantly slower tumor growth rate than did untreated mice. In K562-bearing mice, the tumor weight of berbamine-treated group was lower than that of the control group(1.46g±0.43g vs 2.90g±0.94g, P<0.01 )and the inhibition rate was 49.66%. In Jurkat-bearing mice, the tumor weight of berbamine-treated group was also lower than that of untreated group(0.96g±0.64g vs 2.28g±0.33g, P<0.01), although it was comparable to that of Ara-C-treated group(0.54g±0.38g, P=0.311). The inhibition rates were 57.89% and 76.32% respectively. Moreover, in Jurkat-bearing mice berbamine inhibited the tumor cells invasion into bone marrow. In K562-bearing mice, berbamine down-regulated the expression level of bcr/abl gene of tumor cells ((berbamine-treated group 1.07±0.05 vs untreated group 1.58±0.24, P<0.05). In addition, no harmful side effects were attributed to berbamine.

Conclusion: In vivo, berbamine could aslo take a better antileukemia effect and the dose of berbamine used was safe with almost no side effects in nude mice. Berbamine extracted from Chinese herb might be a promising candidate of new drugs for clinical anticancer treatment, especially for bcr-abl⁺ diseases.