[Alteration of expression of survivin in HL-60 cells treated with chemotherapeutic drugs].

ABSTRACT

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, expressed in the most human cancers but not in terminally differentiated adult tissues, so survivin may be a target for tumor therapy. In addition, some scholars found that survivin expression is associated with the resistance in chemotherapy. To explore the relationship between survivin and drug-resistance, the alteration of survivin mRNA and protein of HL-60 cells treated with daunomycin (DNR), mitoxantrone (MIT) and arsenic trioxide (As2O3) was investigated, the expressions of survivin mRNA and survivin protein were detected on the first and third day by RT-PCR and Western blot, respectively. The results showed that survivin mRNA levels all decreased after the first day of treatment with drugs. It was decreased by 10% in DNR group, 40% (P < 0.01) in MIT group, and 25% (P < 0.01) in As2O3 group in comparison with control cells. In the third day, the survivin mRNA treated with DNR was up-regulated by 20% (P < 0.05), compared with the first day, and MIT was up-regulated by 65% (P < 0.01), but As2O3 was still down-regulated by 32% (P < 0.01). In Western blot, survivin protein level increased 14% after treated with DNR for three days, compared with the control cells, and 11% in MIT, but decreased by 82% in As2O3. It is concluded that after treatment with chemotherapeutic drugs, the survivin level descended at first day and then ascended obviously. This phenomenon may be associated with the resistance in chemotherapy for leukemia. On the other hand, As2O3 shows a different mechanism that may play a significant role to reverse resistance.