Synergistic Inhibitory Effect of Arsenic Trioxide Combined with Itraconazole on Hedgehog Pathway of Multiple Myeloma NCI-H929 Cells / 中国实验血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the antitumor effect of arsenic trioxide (ATO) combined with itraconazole (ITRA) on human multiple myeloma NCI-H929 cells by synergistically inhibiting Hedgehog (HH) signaling pathway.</p><p><b>METHODS</b>The inhibitory rate of NCI-H929 cells was assayed by MTT method. Tumor weight, tumor weight inhibition rate, and tumor volume of mouse model with multiple myeloma were examined. The ELISA were appled to detect the M-protein, qPCR and Western blot were used respectively to detect the expression level of Ptch, SMO, Gli and downstream target genes, the survival rate of tumor-bearing mice was analyzed.</p><p><b>RESULTS</b>ATO combined with ITRA significantly inhibited NCI-H929 cell proliferation as compared with a single administration. The combination of ATO and ITRA could synergistically inhibit tumor growth and obviously reduced tumor burden, survival time of tumor-bearing mice was significantly prolonged. qPCR and Western blot results confirmed that the ATO combined with ITRA could significantly down-regulated expression of Gli1, leading to significantly decrease of cyclinD1 and BCL-2 expression levels.</p><p><b>CONCLUSION</b>ATO combined with ITRA can more strongly suppress the growth of multiple myeloma NCI-H929 cells, as compared with a single administration. The synergistic effect of ATO and ITRA significantly down-regulates expression of Gli1 in HH signaling pathway, moreover the inhibition of target gene overexpression may be one of two drug mechanisms.</p>