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Journal of Chinese Integrative Medicine ›› 2007, Vol. 5 ›› Issue (6): 647-650.doi: 10.3736/jcim20070609

• Original Experimental Research • Previous Articles     Next Articles

Effects of arsenic trioxide on expressions of vascular endothelial growth factor and P-glycoprotein in multidrug resistant leukemia cell line K562/A02

Hong Liang1, Yu Zhang1, Jian-dong Zhang1, Jian Gu2, Li Ma2, Xiao-ling Wang2, Wei-gan Shen1   

  1. 1. Medical College,Yangzhou University,Yangzhou,Jiangsu Province 225001,China
    2. Yangzhou Institute of Hematology,Yangzhou,Jiangsu Province 225001,China
  • Online:2007-11-20 Published:2007-11-15

Objective: To investigate the effects of arsenic trioxide (ATO) on the expressions of vascular endothelial growth factor (VEGF) and P-glycoprotein (P-gp) in K562/A02 cells and to explore the correlation between VEGF and P-gp.Methods: The inhibition rate of K562/A02 cell proliferation was detected by using methyl thiazolyl tetrazolium assay (MTT); the level of VEGF was detected by enzyme-linked immunosorbent assay (ELISA) and the expression rate of P-gp was determined by flow cytometry (FCM).Results: 0.05 μmol/L ATO had no influences on the cell proliferation and the expression of VEGF in K562/A02 cells; 0.4 and 3.2 μmol/L ATO could significantly inhibit the K562/A02 cell proliferation and down-regulate the expression of VEGF in K562/A02 cells (P<0.05). The expression of P-gp did not changed after being exposed to 0.05 and 0.4 μmol/L ATO for 24, 48 and 72 hours (P>0.05). 3.2 μmol/L ATO could remarkably reduce the expression of P-gp in K562/A02 cells after 48- and 72-hour incubation with ATO (P<0.05).Conclusions: The down-regulation of P-gp and VEGF after being exposed to ATO probably contributes to the reversion of multidrug resistance in K562/A02 cells. The level of VEGF may be related to the expression rate of P-gp in K562/A02 cells.

Key words: vascular endothelium, endothelial growth factors, arsenic compounds, leukemia

CLC Number: 

  • R733.7

Figure 1

Inhibition rates of K562/A02 and K562/S cells treated with different concentrations of ATO"

Table 1

Effects of ATO on expression of VEGF in K562/A02 cells (ヌ±S, ng/L)"

Group n The levels of VEGF in different action time
24 h 48 h 72 h
Blank control 6 772.93±22.00 1 137.17±77.85 2 957.23±92.15
0.05 μmol/L ATO-treated 6 785.13±31.85 1 194.63±90.68 3 005.43±111.47
0.4 μmol/L ATO-treated 6 440.13±29.70* 548.07±24.00* 1 741.97±122.45*
3.2 μmol/L ATO-treated 6 199.00±23.79* 410.57±55.99* 1 098.23±73.78*

Table 2

Effects of ATO on expression of P-gp in K562/A02 cells (ヌ±S, %)"

Group n The levels of P-gp in different action time
24 h 48 h 72 h
Blank control 6 61.78±1.33 68.20±1.38 70.31±5.58
0.05 μmol/L ATO-treated 6 61.41±6.01 66.10±2.03 71.96±1.14
0.4 μmol/L ATO-treated 6 62.44±1.68 63.12±2.03 71.02±2.68
3.2 μmol/L ATO-treated 6 63.96±0.91 62.68±1.71* 42.90±3.43*
[1] 陈信义, 刘江涛 . 肿瘤多药耐药性与中药逆转研究[J]. 中西医结合学报, 2003,1(3):221-222
Chen XY, LIU JT . Study on tumor cells’ multidrug resistance and its reversion by Chinese he[J]. Zhong Xi Yi Jie He Xue Bao, 2003,1(3):221-222
[2] Dias S, Shmelkov SV, Lam G , et al. VEGF(165) Promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition[J]. Blood, 2002,99(7):2532-2540
[3] 吕喜英, 李青山, 冯威健 . P-gp和VEGF在非小细胞肺癌中的表达[J]. 临床肺科杂志, 2003,8(4):304-306
Lu XY, Li QS, Feng WJ . The Expression of P-gp and VEGF in Non-small Cell Lung Cancer[J]. Lin Chuang Fei Ke Za Zhi, 2003,8(4):304-306
[4] Malmer B, Brannstrom T, Andersson U , et al. Does a low frequency of P53 and Pgp expression in familial glioma compared to sporadic controls indicate biological differences?[J]. Anticancer Res, 2002,22(6):3949-3954
[5] Koom?gi R, Mattern J, Volm M . Up-regulation of resistance-related proteins in human lung tumors with poor vascularization[J]. Carcinogenesis, 1995,16(9):2129-2133
[6] Volm M , Koom gi R, Mattern J .et al. Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships to drug response in vitro[J]. Anticancer Res, 1997,17(1):99-103
[7] Klement G, Huang P, Mayer B , et al. Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts[J]. Clin Cancer Res, 2002,8(1):221-232
[8] 黄秀榕, 祁明信, 吴正正 , 等. 增殖细胞核抗原法研究莪术和三氧化二砷对晶状体上皮细胞增殖的抑制作用[J]. 中华中医药学刊, 2007,25(2):201-203
Huang XR, Qi MX, Wu ZZ , et al. The Inhibition of Rhizoma Curcumae and Arsenite Trioxide on Proliferation of Lens Epithelial Cell by Detection of Proliferating Cell Nuclear Antigen[J]. Zhong Hua Zhong Yi Yao Xue Kan, 2007,25(2):201-203
[9] 郭宗明, 谢兆霞, 秦忆 . 急性白血病患者VEGF与多药耐药关系的初步探讨[J]. 中国现代医学杂志, 2004,14(5):121-123
Guo ZM, Xie ZX, Qin Y . Relationship between VEGF and MDR in acute leukemia patients[J]. Zhong Guo Xian Dai Yi Xue Za Zhi, 2004,14(5):121-123
[10] 王淑婷, 李清, 刘超 , 等. As2O3逆转K562/ADM细胞多药耐药的研究[J]. 解剖科学进展, 2002,8(3):237-239
Wang ST, Li Q, Liu C , et al. Reversal Effect of As2O3 on Multidrug Resistance K562/ADM Cell Line[J]. Jie Pou Ke Xue Jin Zhan, 2002,8(3):237-239
[11] 李晓明, 韩建群 . vegf和MDR1在急性髓系白血病中的表达及其与预后关系研究[J]. 现代肿瘤医学, 2006,14(2):215-217
Li XM, HAN JQ . Expression of VEGF and MDR1 in acute myeloid leukemia patients and the relation with prognosis[J]. Xian Dai Zhong Liu Yi Xue, 2006,14(2):215-217
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