[Vascular endothelial growth factor antisense oligodeoxynucleotide enhance drug-sensitivity of myeloid leukemia cells to homoharringtonine].

OBJECTIVE

To explore the effects of antisense phosphorothioate oligodeoxynucleotides (AS PS-ODN) of vascular endothelial growth factor (VEGF) on drug-sensitivity of AML and CML cells to homoharringtonine and its possible mechanism.

METHODS

A7, which was the most effective AS PS-ODN selected by computer aid-designing and experimental assay, contains 20-mer modified with phosphorothioate. It was transferred into cells by lipofectin while cultured in 2% serum medium for 8 h and then in 10% serum medium. Twenty four hours later, homoharringtonine was added into the culture and cultured for another 48 h. Cell viability was detected by trypan blue exclusion every 24 hours, cell apoptosis by flow cytometry, and level of VEGF protein by a VEGF ELISA kit.

RESULTS

The combination of A7 and homoharringtonine was able to inhibit cell survival (AML cell survival reduced 38%, CML cell survival reduced 25%), down-regulate VEGF protein expression (VEGF protein expression of AML cell and CML cell declined 25.44% and 30.81%, respectively) and increase homoharringtonine induced apoptosis in both AML and CML cells (apoptotic rates of AML and CML cells increased 48.29% and 52.76%, respectively).

CONCLUSION

The VEGF AS PS-ODN is able to enhance the drug-sensitivity to homoharringtonine, suggesting that inner VEGF proteins in myeloid leukemia cells had a drug-resistant effect.