Department of hematology, Hunan Province People's Hospital, Changsha, Hunan, China.
J Cell Biochem. 2019 Apr;120(4):5620-5627. doi: 10.1002/jcb.27845. Epub 2018 Oct 15.
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.
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.
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.
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.
冬凌草甲素是一种从冬凌草中分离出来的二萜类化合物，具有很强的抗癌活性。丙戊酸（VPA）是一种新兴的抗肿瘤组蛋白去乙酰化酶抑制剂。本研究旨在探讨冬凌草甲素与 VPA 联合抑制人白血病细胞生长和转移的协同作用。
通过 MTT 法评估冬凌草甲素和 VPA 对增殖的影响。通过 Transwell 和划痕实验分别评估细胞迁移和侵袭。此外，通过流式细胞术检测细胞凋亡。通过使用异种移植裸鼠来确定冬凌草甲素和 VPA 的体内抑制作用。
结果表明，冬凌草甲素与 VPA 联合可协同抑制 HL-60 细胞的增殖，并通过激活内在凋亡途径诱导明显的 caspase 依赖性凋亡，这涉及到 Bcl-2/Bax 比值的下调。此外，体内联合治疗显著减小了异种移植肿瘤的大小并触发了肿瘤细胞凋亡。
我们的结果表明，冬凌草甲素加 VPA 的新组合对人髓样白血病细胞具有协同的增殖抑制和诱导凋亡作用，可能是一种有前途的抗白血病策略。
