Effects of artesunate on the proliferation and apoptosis of bortezomib-resistant multiple myeloma cells
10.13699/j.cnki.1001-6821.2018.10.014
- VernacularTitle:青蒿琥酯对硼替佐米耐药的骨髓瘤细胞株增殖与凋亡的影响
- Author:
Rui-Ming OU
1
;
Chang-Hua ZHOU
;
You-Ping TAN
;
Shuang LIU
;
Qi ZHONG
;
Qing ZHANG
Author Information
1. 广东省第二人民医院血液科
- Keywords:
artesunate;
bortezomib;
multiple myeloma;
drug-resistance;
apoptosis
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(10):1183-1186
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of artesunate on the proliferation,cell cycle,apoptosis and apoptosis-related protein of bortezomib-resistant multiple myeloma (MM) cells.Methods Human MM cell line NCI-H929 was treated with bortezomib in a dose-dependent manner to establish a bortezomib-resistant cell line NCI-H929BR.The logarithmic growth phase NCI-H929BR cells were divided into control group(blank culture medium)and two concentration experimental groups (artesunate,25,50 μg · mL-1)and treated for 48 h.The inhibitory role of artesunate on NCI-H929BR proliferation was measured by MTT assay.Cell apoptosis and cell cycle were determined by flow cytometry.The Bcl-2 family proteins (Bcl-2,Bcl-Xl,Bax) were detected by Western blot.Results Bortezomib resistance index of NCI-H929BR is 20.12 times than NCI -H929.After administration artesunate for 48 h,the proliferation rate of NCI-H929BR in the low and high concentration experimental groups were 62.46％,33.48％;there was significant difference compared with control group (all P＜0.05).The artesunate dramatically decreases NCI-H929BR proliferation in a dose-dependent manner (P ＜ 0.05).After treatment for 48 h with artesunate,the proportion of G1 phase cell cycle in high concentration experimental group was increased compared with control group [(51.63 ± 4.02) ％ vs (34.72 ± 2.43) ％,P ＜ 0.05].The proportion of apoptosis cell was increased,early apoptosis in high concentration experimental group and control group were (13.10 ± 1.53)％,(2.32 ± 1.02)％;and late apoptosis in the two groups were (10.26 ±2.42)％,(1.93 ± 0.69) ％;comparison between two groups,the difference had significantly (all P ＜ 0.05).In addition,artesunate significant decreased of Bcl-2 and Bcl-Xl protein expression and increased of Bax protein expression in a dose -dependent manner.Conclusion Artesunate could inhibit NCI-H929BR proliferation,increase apoptosis,cause G0/G1-arrest and down-regulate Bcl-2 and Bcl-Xl expression,while up-regulate Bax expression.
