Inhibiting Effect Of Raddeanin A On Human Hepatic Tumor Transplanted Into Nude Mice And Its Influence On VEGF And HIF-1α Expressions

To study the inhibiting effect and mechanism of Raddeanin A on human hepatoma cells tumor transplanted into nude mice, following with the two areas. Part One. Inhibiting effect of Raddeanin A on human hepatoma cells tumor transplanted tumor into nude mice.Objective: To observe the inhibited effect of Raddeanin A on human hepatoma cells tumor transplanted into nude mice.Methods: The transplanted tumor nude mice were divided into three groups by randomized block method (RaddeaninA, DPP, normal saline). Mice planted with tumor cells 3d later were injected drugs daily: observing tumor size and caculating tumor inhibition rate every two day in the treatment, observing the impact of drugs on the survival rate of nude mice and the change of tumor histopathology.Results:(1) The Raddeanin A had a significant inhibiting effect on transplanted tumor growth in nude mice. There was significant statistical differene on transplanted tumor volume between Raddeanin A, DDP and normal saline on the 10th day of treatment, and the inhibition rate was 68.57% and 63.15% at that day. Along with the treating times, the differences was more significant between Raddeanin A, DDP and normal saline. There was no significantly statistical difference on tumor volume and inhibition rate between Raddeanin A and DDP (P> 0.05). (2) It was found that the Raddeanin A had small bad effect on the nude mice physical: at the end of treatment, survival rate of nude mice in group of Raddeanin A was 100% (8 / 8), the group of DDP was 62.5% (5 / 8). The survival rate of nude mice between Raddeanin A group and the DDP group were significantly statistical difference (P <0.05). (3) The tumor body is smaller and tumor cells were sparse in group of Raddeanin A within pathological observation.Conclusions: (1) We found that Raddeanin A inhibited the proliferation of tumor growth in nude mice and at a certain range the inhibiting effects were depended on the treating times. Raddeanin A has a strong effect on anti-tumor activity and potential medical value. (2) Raddeanin A had small bad effect on the nude mice body, and long-term use was safe and reliable.Part Two. The effect of Raddeanin A on vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α(HIF-1α) expressions in transplanted tumor of nude mice.Objective: To investigate the mechanism of Raddeanin A on hepatic cancer treatment.Methods: RT-PCR was used to detect mRNA levels of VEGF and HIF-1αin tumor of nude mice of Raddeanin A group, DDP group and normal saline group. The protein lever of VEGF and HIF-1αin tumor of nude mice of every group was detected by immunohistochemistry .Results: (1) The mRNA exppression of VEGF and HIF-1αin tumor tissue was decreased after the treatment of Raddeanin A .There was significant difference between the Raddeanin A group and the negative control group on the expression of mRNA levels of VEGF and HIF-1α(F=9.918,P=0.002,F=12.562,P=0.001); But there was no statistical difference between the Raddeanin A group and DDP group on the expression of mRNA levels of VEGF and HIF-1α(P >0.05); (2) It was found that expression of protein VEGF and HIF-1αin Raddeanin A group and DDP group were lower than normal saline group, and the differences was significant(H=7.075,P=0.029,H=10.598,P=0.005). Conclusions: (1) Expression of HIF-1αmRNA and VEGF mRNA in tumor tissue of nude mice can be inhibited by Raddeanin A. (2) Expression of protein HIF-1αand VEGF in tumor tissue of nude mice can be inhibited by Raddeanin A. (3) Inhibition on the growth neovascularization would be one of important mechanisms of Raddeanin A suppressing growth of hepatic cancer.