Study on the mechanism of Guizhi-Fuling pill intervention for epithelial ovarian carcinoma in nude mice

Abstract

Objective To observe the effect of Guizhi-Fuling pill on the expression of transcription factor Twist-1, CD133, vascular endothelial growth factor(VEGF)and hypoxia-inducible factor-1α(HIF-1α)in the epithelial ovarian cancer of nude mice. Methods A total of 48 nude mice were randomly divided into the control group, the model group, the Guizhi-Fuling pill low- and high- dose groups. The model group, Guizhi-Fuling pill low- and high- dose group were treated by the intraperitoneal injection of HeyA8 ovarian cancer cell lines in nude mice for the ovarian cancer model. Second days Guizhi-Fuling low- and high-dose group were given 0.03, 0.15 g/kg Guizhi-Fuling pill. The control group and the model group were given equal valume saline. After the intervention of 21 days, the expression of Twist-1 and CD133 were determined by immunohistochemical staining method. The expression of VEGF and HIF-1α protine in the nude mice ovarian tissue were mesured by the enzyme linked immunosorbent assay(ELISA)method. The content of IL-2, IL-12 in peritoneal fluid were determined. Results Compared with the model group, the expression of Twist-1(61.32% ± 4.12% vs. 86.01% ± 7.90%), VEGF(55.51 ± 4.84 pg/ml vs. 75.12 ± 6.04 pg/ml), VEGF mRNA(3.70 ± 0.51 vs. 5.04 ± 0.33), HIF-1α(9.81 ± 0.65 ng/ml vs. 17.74 ± 1.31 ng/ml), HIF-1 mRNA(1.05 ± 0.10 vs. 2.31 ± 0.30)in peritoneal tumor tissue of Guizhi-Fuling pill high dose group were decreased significantly(P<0.05).The content of IL-2(7.94 ± 0.67 U/L vs. 13.30 ± 1.24 U/L), and the level of IL-12(0.32 ± 0.04 U/L vs. 0.78 ± 0.06 U/L)in peritoneal fluid of Guizhi-Fuling pill high dose group were decreased significantly(P<0.05). Conclusion Guizhi- Fuling pill by downregulating the expression of Twist-1, VEGF and HIF-1α, and decreasing levels of IL-2 and IL-12, showed its effect on epithelial ovarian cancer in nude mice. Key words: Gui Zhi Fu Ling Wan; Ovarian neoplasms; Vascular endothelial growth factor; Transcription factors; Mice, nude