The Experimental Study Of Treatment For The Implanted VX2 Liver Tumor In Rabbits Percutaneous Intratumor AiDi Injection

Objective: To investigate the anti-cancer effect of ultrasound-guided intra-tumoral injection of traditional Chinese medicine"AiDi injection"in the treatment of hepatocellular carcinoma (HCC) and to determine whether"AiDi injection"has obvious adverse effects on the body,so as to search for a new pathway of drug administration for the treatment of HCC with AiDi injection.Methods:New Zealand rabitts were implanded VX2 tumor tissue into there livers to establish tomoral models in the comparative experiment for different dose of AiDi injection .15ingle-lesion models were divived into 3 groups randomly and 5 rabitts in each group .The tumor foci in the three groups were performed AiDi injection with 0.3ml,0.5ml,1ml for every once respectively and once for every 3 days,After 4 jection the rabitts were killed. the rates of tumor necrosis and the growth rate of the tumor was calculated.In control experiment, twenty eight New Zealand White rabbits with implanted liver VX2 tumors were randomly divided into three groups, a Isotonic saline group(n=8), a PEI group(n=8),and an PADI group (n=12) .Three weeks after transplantation the study medicine were injected into tumors of all the rabbits once every 3 days .After 4 injection the rabbits were killed.The 3 dimensions of the tumors were measured by CT and the rates of tumor necrosis,the volume of tumor,the growth rate of the tumor was calculated.Liver and kidney function tests (AST, ALT,ALP and BUN ) as well as white blood cell counts were determined before and after treatment, CT examination was performed at the same time. Themorphological and the ultramicrostructural changes and hepatic tissue were also investigated under light microscope or electron microscope. Apoptotic cells were evaluated by TUNEL essay.Vascular endothelial growth factor (VEGF) andexpression were examined by immunohistochemistry.Results:1. There are no evident changes of liver and kidney function before and after treatment in the 3 groups (P>0.05) .2. PADIgroup:The necrotic lesion showed hypoattenuate without enhancement and clear margin in CT scanning , Peripheral enhancement of the hepatic parenchyma surrounding the lesion was seen in arterial phase. PEI group: radiological appearances is homoplastic to PADI group. Isotonic saline group : inhomogeneous enhancement of the hepatic parenchyma was seen in arterial phase. 3. Tumors in all groups kept growing after the procedure. For PADI group,the growing rate was the lowest and the necrotic rate was the highest .Significant difference in the growing rate and necrotic rate existed between PADI group and saline group (p<0.05),while no significant difference was found between PADI group and PEI group (p>0.05).4. TUNEI essay: Apoptotic index (AI) in PADI group was significantly higher than those of ethanol group and saline group . positive correlation (p<0.05).5. Histopathological changes: After PADI,the necrosis became larger with massive granulation and fibrous hyperplasia under light microscope, the residual tumor cells swelling and degenerating,massiv lymphocytes infiltration at the edge of the necrosis lesion;In the PEI roup, the coagulation necrosis was massive and the granulation and fibrous hyperplasia were less.in electron microscope massive dissolution necrosis of tumor cells,many apoptosis cells and apoptotic bodys,swelling mitochondrial,dilated endoplastic reticulum,accummulated lipid was occurred in the area of injection after PADI.In the PEI group, the large central coagulationnecrosis appeared,the electron density decreased and less apoptosia bodies.6. The expression of VEGF protein was statistically lowest of the PADI group(P<0.05), The expression of VEGF protein in the PEI group was ower than that of the saline group. Conclusions:1. PADI can obviously inhibit and destroy the liver VX2 tumor cells, the effect Get close to ethanol, and without abvious toxicity or side effects.2. AiDi injection can induce the liver VX2 tumor cells apoptosis.3. AiDi injection can inhibite the expression of VEGF of in the liver VX2 tumors tissue.4. AiDi injection is possible to enhance immunological function of organism, but it need to be confirmed further.