Background: Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activities. Valproic acid (VPA) is a recently emerged antineoplastic histone deacetylase inhibitor. The aim of the present study is to investigate the synergistic role of oridonin and VPA to inhibit the growth and metastasis of human leukemia cells.
Methods: The effect of oridonin and VPA on proliferation was evaluated by the MTT assay. Cell migration and invasion were evaluated by transwell and scratch assays, respectively. In addition, cell apoptosis was examined by flow cytometry. The inhibitive effects of oridonin and VPA in vivo were determined by using xenografted nude mice.
Results: The results demonstrated that oridonin in combination with VPA synergistically inhibited the proliferation of HL-60 cells, and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway, which is involved in the downregulation of Bcl-2/Bax ratio. Furthermore, the combination treatment in vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis.
Conclusion: Our results suggested that the novel combination of oridonin plus VPA exerted synergistic antiproliferative and apoptosis-inducing effects on human myeloid leukemia cells, and may serve as a potentially promising antileukemia strategy.
Keywords: Notch signaling pathway; cell apoptosis; leukemia; oridonin; valproic acid (VPA).
© 2018 Wiley Periodicals, Inc.