title: Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells.
abstract: Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated fromRabdosia rubescenswith potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML) cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridoninin vivowas determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cellsin vitroandin vivo. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.
authors.affiliation: Department of Haemal Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Haemal Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Haemal Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Youmei
authors.initials: Y
authors.lastname: Zi
authors.affiliation: Department of Haemal Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Lingxiu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Haemal Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Haemal Internal Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
keywords: Acute myeloid leukemia; Cell apoptosis; Cisplatin; Drug resistance; Oridonin