[Inhibition effect of topotecan on human myelodysplastic syndrome cells in vitro and in vivo]

Abstract

Objective: To investigate the effect of topotecan (TPT) on human myelodysplastic syndrome (MDS) cells in vitro and in vivo.

Methods: Cell growth was measured by a MTT assay. The percentage of cells undergoing apoptosis was determined by flow cytometry after staining with annexin V-FITC and propidium iodide. The morphology of apoptotic cells was observed by transmission electron microscopy (TEM). Furthermore, the antitumor effect on MDS cells in xenotransplanted severe combined immunodeficiency (SCID) mice was evaluated by tumor volume and survival. Western blot was used for determining the expression of topoisomerase I (Top1) protein.

Result: The growth of Mutz-1 cells was suppressed by TPT treatment in a dose-dependent manner. The 50% inhibition in Mutz-1 cell growth (IC(50)) of TPT for 72 h was 272 ng/L. The percentage of apoptotic cells observed in the Mutz-1 cells after exposure to TPT (160 ng/L) in 48 h and 72 h was (54.16 +/-4.29)% and (72.97+/-6.12)%, respectively. TEM showed the characteristics of apoptosis in Mutz-1 cells treated with TPT. The xenotransplanted SCID mice treated with TPT showed inhibited tumor growth compared with control group. TPT treatment resulted in a longer survival as compared with the control group (P<0.001) and with the As2O3-treated group (P<0.001). The cells exposed to TPT exhibited a time-dependent decrease of Top1 protein expression.

Conclusion: TPT can inhibit Mutz-1 cell growth and induce apoptosis in vitro.The downregulation of Top1 may be involved in the apoptosis induced by TPT. TPT has a significant antitumor effect in vivo.