ABSTRACT
To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and cirrhosis.
Subject(s)
Animals , Male , Rats , Actins , Metabolism , Alanine Transaminase , Blood , Antineoplastic Agents , Pharmacology , Aspartate Aminotransferases , Blood , Bile , Chemistry , Bilirubin , Blood , Body Weight , Carcinoma, Hepatocellular , Blood , Pathology , Diethylnitrosamine , Liver , Metabolism , Pathology , Liver Cirrhosis , Pathology , Liver Neoplasms, Experimental , Blood , Pathology , Powders , Pharmacology , Proliferating Cell Nuclear Antigen , Metabolism , Random Allocation , Rats, Sprague-Dawley , UrsidaeABSTRACT
<p><b>OBJECTIVE</b>To explore the efficacy of intraperitoneally injected epirubicin (EPI)-loaded poly (d, l)-lactic acid (PLA) microspheres (MS) alone or combined with free epirubicin (FEPI) in treating hepatocellular carcinoma (HCC) in mice.</p><p><b>METHODS</b>Mice that were transplanted with H22 ascites HCC were randomized into seven groups, which were intraperitoneally injected with blank microspheres, normal saline, three different doses of microspheres (9, 18, and 36 mg/kg EPI) , FEPI (9 mg/kg) , and the combination (microspheres with EPI 4.5 mg/kg + FEPI 4.5 mg/kg). The survival time of all animals was recorded. The rates of increase in life span of all the treatment groups were calculated.</p><p><b>RESULTS</b>EPI-PLA-MS significantly prolonged the survival time of HCC mice in a dose-dependent manner, with a maximal tolerated dose (MTD) of 18 - 36 mg/kg. The combination group had the highest average survival time, median survival time, and rate of increase in life span, which were (40.0 +/- 16.9) days, 33.5 days, and 222.58%, respectively.</p><p><b>CONCLUSION</b>EPI-PLA-MS combined with FEPI is highly effective in treating HCC in mice when intraperitoneally injected.</p>
Subject(s)
Animals , Male , Mice , Delayed-Action Preparations , Epirubicin , Therapeutic Uses , Infusions, Parenteral , Lactic Acid , Liver Neoplasms, Experimental , Drug Therapy , Microspheres , Polyesters , PolymersABSTRACT
<p><b>OBJECTIVE</b>To study the effectiveness of treating hepatocellular carcinoma (HCC) in mice with locally administered epirubicin-loaded poly( D, L) - lactic acid microspheres (EPI-PLA-MS ).</p><p><b>METHODS</b>EPI-PLA-MS was prepared with double emulsion solvent evaporation technique. Five groups of mice (n = 8 in each group) were intraperitoneally injected with five different doses of free epirubicin (FEPI), and the maximum tolerated dose (MTD) was calculated. Then 15 mice with transplanted subcutaneous H22 HCC were divided into three groups (n = 5), which were respectively intratumorally injected with normal saline (NS), blank microspheres, and EPI-PLA-MS (with 9 mg/kg of EPI). After two weeks the tumors were excised and weighed. Another 15 mice with transplanted H22 ascites HCC were divided into three groups (n = 5), which were intraperitonealy injected with the same drugs, and the increased life span were registered exactly.</p><p><b>RESULTS</b>The MTD of intraperitoneally injected FEPI was 9 mg/kg. The tumour-inhibiting rates was 40.35% and 36.09% when EPI-PLA-MS were administered by intratumoral injection to the mice with subcutaneous H22 HCC. It significantly prolonged the survival time of mice with H22 ascites HCC and the increased life span by 153.49% and 142.22% when EPI-PLA-MS were intraperitoneally administered.</p><p><b>CONCLUSION</b>EPI-PLA-MS is a new sustained-release preparation with high-efficacy and low-toxicity in treating HCC and has shown promising prospects when administered locally.</p>