Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2012; 18(47): 7079-7086
Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.7079
Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice
Qing-E Tian, Huan-De Li, Miao Yan, Hua-Lin Cai, Qin-You Tan, Wen-Yuan Zhang
Qing-E Tian, School of Pharmaceutical Sciences, Central South University, Changsha 410011, Hunan Province, China
Qing-E Tian, Xiangtan Central Hospital, Xiangtan 411100, Hunan Province, China
Qing-E Tian, Huan-De Li, Miao Yan, Hua-Lin Cai, Qin-You Tan, Wen-Yuan Zhang, Clinical Pharmacy and Pharmacology Research Institute, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Author contributions: Tian QE drafted the manuscript and made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data; Li HD made substantial contributions to conception and design; Yan M, Cai HL, Tan QY and Zhang WY drafted the manuscript and revised it critically for intellectual content.
Correspondence to: Huan-De Li, Professor, Clinical Pharmacy and Pharmacology Research Institute, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road Changsha, Changsha 410011, Hunan Province, China. tqedkj@163.com
Telephone: +86-731-85292121 Fax: +86-731-84436720
Received: April 7, 2012
Revised: June 18, 2012
Accepted: August 3, 2012
Published online: December 21, 2012
Abstract

AIM: To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.

METHODS: To establish a solid tumor model, 5.0 × 106/mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice (6-12 wk old, 18-22 g). When the tumors reached a size of 100 mm3, the animals were treated as indicated, and the mice were randomly assigned to seven groups (n = 10 each). After ten days of treatment, blood samples were collected from mouse eyes, and serum was harvested by centrifugation. Mice were sacrificed, and the whole body, tumor, spleen and thymus were weighed immediately. The rate of tumor inhibition and organ indexes were calculated. The expression levels of serum cytokines, P-glycoprotein (P-GP) and multidrug resistance (MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay, Western blotting, and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction, respectively.

RESULTS: The tumor inhibition rates in the treatment groups of Adriamycin (ADM) + Astragalus polysaccharides (APS) (50 mg/kg), ADM + APS (100 mg/kg), and ADM + APS (200 mg/kg) were significantly higher than in the ADM group (72.88% vs 60.36%, P = 0.013; 73.40% vs 60.36%, P = 0.010; 77.57% vs 60.36%, P = 0.001). The spleen indexes of the above groups were also significantly higher than in the ADM group (0.65 ± 0.22 vs 0.39 ± 0.17, P = 0.023; 0.62 ± 0.34 vs 0.39 ± 0.17, P = 0.022; 0.67 ± 0.20 vs 0.39 ± 0.17, P = 0.012), and the thymus indexes of the ADM + APS (100 mg/kg) and ADM + APS (200 mg/kg) groups were significantly higher than in the ADM group (0.20 ± 0.06 vs 0.13 ± 0.04, P = 0.029; 0.47 ± 0.12 vs 0.13 ± 0.04, P = 0.000). APS was found to exert a synergistic anti-tumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD. The expression of interleukin-1α (IL-1α), IL-2, IL-6, and tumor necrosis factor-α (TNF-α) was significantly higher in the ADM + APS (50 mg/kg), ADM + APS (100 mg/kg) and ADM + APS (200 mg/kg) groups than in the ADM group; and IL-10 was significantly lower in the above groups than in the ADM group. APS could increase IL-1α, IL-2, IL-6, and TNF-α expression and decrease IL-10 levels. Compared with the ADM group, APS treatment at a dose of 50-200 mg/kg could down-regulate MDR1 mRNA expression in a dose-dependent manner (0.48 ± 0.13 vs 4.26 ± 1.51, P = 0.000; 0.36 ± 0.03 vs 4.26 ± 1.51, P = 0.000; 0.21 ± 0.04 vs 4.26 ± 1.51, P = 0.000). The expression level of P-GP was significantly lower in the ADM + APS (200 mg/kg) group than in the ADM group (137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg, P = 0.023).

CONCLUSION: APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice. This may be related to its ability to enhance the expression of IL-1α, IL-2, IL-6, and TNF-α, decrease IL-10, and down-regulate MDR1 mRNA and P-GP expression levels.

Keywords: Astragalus polysaccharides; Tumor inhibition rate; Cytokines; P-glycoprotein; Adjunct anticancer