Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice

AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /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 mm 3,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 antitumor 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 downregulate 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 IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.

Effect of grape proanthocyanidins on tumor growth and angiogenesis in H22 liver cancer xenograft model

Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.

Inhibitory Effect of Buddlejasaponin Ⅳ on Hepatocarcinoma 22(H_(22)) in Mice

[Objective] This study aimed to investigate the inhibitory effect of buddle- jasaponin IV on growth of hepatocarcinoma 22 （H22） tumor in mice. [Method] The H= tumor cells were transplanted in the right axillary skins of mice. The tumor- bearing mice were randomly divided into five groups, including control group, CTX group （20.0 mg/kg） and buddlejasaponin IV treatment groups （0.25, 0.50 and 1.00 mg/kg）. There were 10 mice in each group. During the treatment, the body weights and survivals of mice in all groups were recorded. The buddlejasaponin IV was in- jected into the abdominal cavities of mice, which lasted for 10 consecutive days. All the mice were slaughtered the next day. The tumors in the abdominal cavities were tanked out and weighed. The tumor inhibition rate, spleen index and thymus index, as well as SOD activity, MDA content, GGT activity and AKP activity in serum were determined. [Result] Compared with the control group, the high- and middle- dosage buddlejasaponin IV treatment groups all showed significant （P〈0.01） inhibito- ry effects on transplanted H22 tumor in mice with tumor inhibition rates of 56.96% and 50.63%, respectively. Compared with those in the control group, the SOD ac- tivity of mice in the high-dosage buddlejasaponin IV treatment group was significant- ly increased （P〈0.05）, and the MDA contents, GGT and AKP activities in mice in the high-, middle- and low-dosage buddlejasaponin IV treatment groups were all sig- nificantly reduced （P〈0.01）. There were no significant differences in all the indexes, except SOD activity, between the CTX and control groups. [Conclusion] Buddlejas- aponin IV has certain inhibitory effect on H22 tumor, of which the mechanism might be related to antioxidation capacity in body.