Effect Of Ginsenoside Rg3 Combined With 5-Fluorouracil On Apoptosis And Angiogenesis Of Transplanted Hepatocellular Carcinoma In Mice

Objective: Hepatocellular carcinoma(HCC) is one of the commonest malignant tumors in the world. It develops rapidly with high mortality. The poorly prognosis is related to early recurrence and metastasis of HCC. The molecule mechanism of Hepatocarcinogenesis, development, recurrence and metastasis are very complicated and not well understood. Abnormal apoptosis and angiogenesis of HCC are considered play an important role in hepatocarcinogenesis and development, recurrence and metastasis. Recent studies suggest that suppressor gene, protein of apoptosis, death protease of effect cells in apoptosis and angiogenic factors of HCC may play a crucial role. In the course of cancer treatment, HCC is insensitive on conventional chemotherapeutic drugs with low tolerance and worse therapeutic effects. Ginsenoside Rg3 is effective composition isolated from the red ginseng. Anti-tumor effect of ginsenoside Rg3 has been confirmed in many studies. 5-Fluorouracil (5-FU) is one of the widely used chemotherapy drugs with HCC, but its effectiveness was not ideal. Some experiments found that ginsenoside Rg3 combined with 5-fluorouracil can enhanced anti-tumor effect and reduce side effects of chemotherapeutic drugs. In order to study the role and mechanism of ginsenoside Rg3 combined with 5-fluorouracil in HCC therapy, we took advantage of a mouse translplanted HCC model induced by H22 cell injection. The purposes are to observe and compare the effects of ginsenoside Rg3, 5-FU and ginsenoside Rg3 combined with 5-FU on apoptosis and angiogenesis of transplanted hepatocellular carcinoma in mice; and explore the anti-tumor mechanism of ginsenoside Rg3.Methods:â‘ 140 mouse of kunming species, with equal ratio of male and female, according to weight, were randomly divided into 5 groups: normal control group(20), HCC model group(30), 5-FU group(30), ginsenoside Rg3 group(30), ginsenoside Rg3 combined with 5-FU(30). H22 cells were injected to liver tissue to form transplanted HCC model in mice. After 24 hours of injection, ginsenoside Rg3 group was orally injected into the stomach for administration, 5-FU group was administrated by intraperitoneal injection, ginsenoside Rg3 combined with 5-FU group was orally injected into the stomach and peritoneal for administration. After 10 days of administration, all mouse were killed and collected liver tissues for detection.â‘¡Immunohistochemical observed the expression of Survivin,Caspase-3,VEGF in liver tissues.Results:â‘ No expression of Survivin was in normal control group; The expression of Survivin of HCC tissues of 5-FU group, ginsenoside Rg3 group and ginsenoside Rg3 combined with 5-FU group were all lower than HCC model group(P<0.05); the expression of Survivin of HCC tissues of ginsenoside Rg3 combined with 5-FU group was lower than 5-FU group(P<0.05) and ginsenoside Rg3 group(P<0.05); In expression of Survivin of HCC tissues, there was no significant difference between 5-FU group and ginsenoside Rg3 group (P>0.05).â‘¡The expression of Caspase-3 of hepatic tissues of normal control group was significantly higher than HCC tissues of HCC model group(P<0.05); the expression of Caspase-3 of HCC tissues of 5-FU group, ginsenoside Rg3 group and ginsenoside Rg3 combined with 5-FU group were all higher than HCC model group(P<0.05); the expression of Caspase-3 of HCC tissues of ginsenoside Rg3 combined with 5-FU group was higher than ginsenoside Rg3 group ( P<0.05 ) ; the expression of Caspase-3 of HCC tissues of 5-FU group was higher than ginsenoside Rg3 group(P<0.05); In expression of Caspase-3 of HCC tissues, there was no significant difference between 5-FU group and ginsenoside Rg3 combined with 5-FU group(P>0.05).â‘¢The expression of VEGF of hepatic tissues of normal control group was significantly lower than HCC tissues of HCC model group(P<0.05); the expression of VEGF of HCC tissues of 5-FU group, ginsenoside Rg3 group and ginsenoside Rg3 combined with 5-FU group were all lower than HCC model group(P<0.05); the expression of VEGF of HCC tissues of ginsenoside Rg3 combined with 5-FU group was lower than 5-FU group (P<0.05); the expression of VEGF of HCC tissues of ginsenoside Rg3 group was lower than 5-FU group(P<0.05); In expression of VEGF of HCC tissues, there was no significant difference between ginsenoside Rg3 group and ginsenoside Rg3 combined with 5-FU group(P>0.05).Conclusions:â‘´Application of ginsenoside Rg3 combined with 5-FU can significantly decrease the expression of Survivin and raise the expression of Caspase-3 to induce apoptosis of hepatoma cells, decrease the expression of VEGF to inhibit angiogenesis of HCC.(2) Ginsenoside Rg3 and 5-FU have all certain function to induce apoptosis of hepatoma cells and inhibit angiogenesis of HCC, but application of ginsenoside Rg3 combined with 5-FU has more significant effect of inducing apoptosis of hepatoma cells than single ginsenoside Rg3 and 5-FU, inhibiting angiogenesis of HCC than single 5-FU.