Study Of Anti-tumor Effects Of Silybinin On Rat Experimental Hepatocellular Carcinoma

Objective: To investigate the anti-tumor effects of Silybinin (SB) on induced rat model of hepatocellular carcinoma (HCC) and its possible mechanism.Methods: Diethylnitrosamine (DENA)-induced rat model of HCC was established by using a modifier method. All rats were randomly divided into SB low-dose group (200μg/ml), SB middle-dose group (1000μg/ml), SB high-dose group (5000μg/ml) and control group (equal volume of sterile water), received free drinking water mixed with the drug. During the experimental period, survival situation of rats was dynamically observed. After 8-week drug treatment, all rats were sacrificed and tumor growth and metastasis were examined. Liver and lung specimens were stained by HE to observe the pathomorphological changes as routine. The levels of hypoxia-inducible factor 1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), Ki-67 and caspase-3 proteins and mRNAs were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Additionally, one-way ANOVA,χ2 test and Kaplan-Meier method were used to statistically analyze the corresponding data.Results: Compared with the control group (69.2%), SB-treated rats had higher survival rate (92.9%, 85.7% and 71.9%); The mean liver weight index (4.56%±0.40%,4.98%±0.50% and 9.28%±1.91%), the mean liver nodules (6.13±0.21),(7.67±0.82), (11.76±2.15); the mean lung nodules (0.51.±0.21) , (0.78±0.13), (3.11.±0.37) ; the lung metastsis rate ((15.4%,25.0% and 50%), and the intratumoral microvessel density (MVD) (0.56±0.11,0.62±0.18 and 2.31±0.64 ) were lower in rats treated with SB than those in control group, which were 14.25%±3.90%, 19.32±3.31, 4.81.±0.53 and 55.6% respectively (P <0.01 or P <0.05). HIF-1α, VEGF, and Ki67 proteins and VEGF mRNA were more obviously downregulated in SB-treated rats than those in control rats, while Caspase-3 protein was statistically increased. Moreover, the level of HIF-1αmRNA had no difference compared between SB groups and control group.Conclusions: Silibinin can obviously inhibit tumor growth and metastasis of HCC. The possible associated mechanisms are as follows: (1) Inhibition of tumor growth and metastasis through antiangiogenesis; (2) Inhibition of tumor growth through blockage of cell proliferation; (3) Exerting antitumor effects through induction of cell apoptosis.