OBJECTIVETo assess the effects of aspirin on the proliferation and apoptosis of human HCC cells.

METHODSThe effects of aspirin on the synthesis of DNA in SMMC-7721 HCC cells were determined by using (3)H-thymidine incorporation. Apoptosis of SMMC-7721 was studied by observation of morphologic changes, Tunnel method and flow cytometry after treatment with aspirin. We also assessed the effects of aspirin on the growth of HCC xenografts in nude mice in vivo.

RESULTSA dose-dependent suppression (r=-0.918, P<0.01) of (3)H-TdR incorporation in HCC cell line treated with aspirin was observed in the concentration range of 1 10(-1)~10(-7)mol/L. The mean tumor volume and weight in nude mice treated with aspirin were significantly lower than those of the control group. The inhibiting rate for HCC xenografts was 71.62% in the aspirin group. After exposure to aspirin (31 10(-3)mol/L) for 48 hours, HCC cells presented some morphologic features of apoptosis. The apoptosis index was markedly higher in the aspirin group (8.90% 1.32%) than in the control group (0.50% 0.35%, P<0.01). A typical subdiploid peak before G0/G1 phase with an apoptosis rate as 12.79% was also observed.

CONCLUSIONSAspirin inhibits the proliferation and increases the apoptosis of human HCC cells not only in vitro but also in vivo.

Animals ; Apoptosis ; drug effects ; Aspirin ; therapeutic use ; Cell Division ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Mice ; Mice, Nude

antibody against tumor specific surface membrane protein was produced by immunizing a New Zealand White rabbit with antigen (66 kDa) prepared from the plasma membrane of rat hepatoma induced by feeding a diet containing 3'-methyl-4-dimethylaminoazobenzene, and was purified by protein A-Sepharose 6MB affinity chromatography. The purified antibody was incorporated into liposomes by a reverse phase evaporation vesicle method in order to prepare a tumor specific anticancer drug carrier. The effect of the antibody against tumor specific antigen was evaluated by comparing the inhibition of DNA synthesis in hepatoma cells with different preparations of methotrexate. Methotrexate encapsulated into liposome showed a stronger inhibitory effect on DNA synthesis (1.4-1.7 times) than free methotrexate. Liposomes having the antibody showed stronger inhibitory effect (3.1 times) on DNA synthesis than free methotrexate group in hepatic nodular area. From these results, it is concluded that tumor specific antibody inserted into liposomal membrane would be recognized by surface antigens which were expressed on the plasma surface membrane of rat hepatoma cells and thereby increase the carrying efficiency of drugs to the target cells. This could be useful in cancer chemotherapy.
Animal ; Antibodies, Neoplasm ; Antigens, Neoplasm/*immunology ; Antigens, Surface/*immunology ; Drug Carriers ; Liposomes ; Liver Neoplasms, Experimental/*drug therapy ; Male ; Methotrexate/*administration and dosage ; Rats ; Support, Non-U.S. Gov't

antibody against tumor specific surface membrane protein was produced by immunizing a New Zealand White rabbit with antigen (66 kDa) prepared from the plasma membrane of rat hepatoma induced by feeding a diet containing 3'-methyl-4-dimethylaminoazobenzene, and was purified by protein A-Sepharose 6MB affinity chromatography. The purified antibody was incorporated into liposomes by a reverse phase evaporation vesicle method in order to prepare a tumor specific anticancer drug carrier. The effect of the antibody against tumor specific antigen was evaluated by comparing the inhibition of DNA synthesis in hepatoma cells with different preparations of methotrexate. Methotrexate encapsulated into liposome showed a stronger inhibitory effect on DNA synthesis (1.4-1.7 times) than free methotrexate. Liposomes having the antibody showed stronger inhibitory effect (3.1 times) on DNA synthesis than free methotrexate group in hepatic nodular area. From these results, it is concluded that tumor specific antibody inserted into liposomal membrane would be recognized by surface antigens which were expressed on the plasma surface membrane of rat hepatoma cells and thereby increase the carrying efficiency of drugs to the target cells. This could be useful in cancer chemotherapy.
Animal ; Antibodies, Neoplasm ; Antigens, Neoplasm/*immunology ; Antigens, Surface/*immunology ; Drug Carriers ; Liposomes ; Liver Neoplasms, Experimental/*drug therapy ; Male ; Methotrexate/*administration and dosage ; Rats ; Support, Non-U.S. Gov't

OBJECTIVETo study the therapeutic effect of intravenous high-dose vitamin C on implanted hepatoma in rats.

METHODSThe rats bearing implanted Walker-256 hepatoma were treated with high-dose vitamin C at 2.83 and 5.65 g/kg intravenously, and the general condition, liver functions (A/G, ALT, AST, GGT), tumor volume, and tumor growth of the rats were evaluated.

RESULTSThe A/G of the rats treated with 2.83 g/kg vitamin C was significantly higher, but the ALT and GCT were significantly lower than those of the model rats (P<0.05 or 0.01). The ALT level in rats with 5.65 g/kg vitamin C treatment was significantly lower than that of the model rats (P<0.05). The tumor necrosis rate was significantly higher in rats with 2.83 g/kg vitamin C treatment than in the model rats (P<0.05).

CONCLUSIONIntravenous administration of 2.83 g/kg vitamin C can promote the necrosis and apoptosis of hepatoma Walker256 cells in rats and protect the liver function of the tumor-bearing rats.

Animals ; Apoptosis ; drug effects ; Ascorbic Acid ; administration & dosage ; Injections, Intravenous ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Male ; Necrosis ; Neoplasm Transplantation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

OBJECTIVETo investigate the inhibitory effect of matrine on tumor growth in tumor-bearing mice and explore its possible mechanisms of anti-tumor action in vivo.

METHODSHepatocellular carcinoma cells H(22) were subcutaneously injected into BALB/c mice and matrine was administered to the tumor-bearing mice. The kinetics of tumor formation and tumor growth were measured, tumor growth inhibition rate (IR) was calculated, and tumor tissue samples were taken and examined by light and electron microscopy to assess the inhibitory effects of matrine on tumor growth in the mice.

RESULTSMarked inhibitory effect of matrine on the transplanted hepatocellular carcinoma H(22) was observed in the tumor-bearing mice. The inhibitory rates were 62.5% and 60.7% in the groups treated with high and low dosage of matrine, respectively (P < 0.01 vs. control group). The tumor formation was significantly retarded and tumor growth was inhibited in matrine-treated groups compared with those in control mice. Histopathological examination revealed widespread necrosis with massive accumulation of infiltrating lymphocytes and plasmacytes in the tumors. Numerous apoptotic cells and apoptotic bodies were observed in the tumors under the electron microscope.

CONCLUSIONMatrine has marked inhibitory effects on tumor growth in vivo, which is probably related to inhibition of cell division and tumor cell proliferation, directly killing of tumor cells and/or induction of apoptosis and modulation of anti-tumor immune responses.

Alkaloids ; therapeutic use ; Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; drug effects ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Quinolizines ; therapeutic use

Animals ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Arsenicals ; therapeutic use ; Fluoresceins ; Liver Neoplasms, Experimental ; chemically induced ; drug therapy ; Male ; Oxides ; therapeutic use ; Rats

OBJECTIVETo investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model.

METHODSVX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis.

RESULTSThe growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05].

CONCLUSIONAs2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.

Animals ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Embolization, Therapeutic ; Emulsions ; pharmacology ; Ethiodized Oil ; pharmacology ; Liver Neoplasms, Experimental ; drug therapy ; Oxides ; pharmacology ; Rabbits ; Tomography, Spiral Computed

Animals ; Antineoplastic Agents ; therapeutic use ; Chromans ; therapeutic use ; Diethylnitrosamine ; Ligands ; Liver Neoplasms, Experimental ; chemically induced ; drug therapy ; Male ; PPAR gamma ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Thiazolidinediones ; therapeutic use

Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Liver Neoplasms, Experimental ; drug therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Radiation-Sensitizing Agents ; therapeutic use ; Taxoids ; therapeutic use

OBJECTIVETo research the microemulsion preparation of Ganoderma lucidum polysaccharides and triterpenes and investigate its properities. Evaluate the effects of polysaccharides and triterpenes microemulsions against transplant tumor growth.

METHODThe microemulsion formula was optimized by constructing the pseudo-ternary phase diagrams of blank microemulsion. The polysaccharides and triterpenes microemulsions were prepared on the blank microemulsions. The appearance, particle distribution and Zeta potential were investigated by transmission electron microscope and grain size analyzer. The Heps mice were randomly administered with polysaccharides and triterpenes microemulsions (114.5, 57.25 mg x kg(-1) x d(-1)) for 7 days. The effectiveness was assessed based on tumor inhibitory ratio of mice with Heps tumors. The toxicity was evaluated by measurements of the mice weight, immune organ weight.

RESULTThe optimal microemulsion formula was composed of tween 20, dimethyl carbinol, water and 9-octadecenoic acid with the ratio of 14.3: 14.3: 33. 3:2. Polysaccharides and triterpenes microemulsions in transmission electron microscope were consisted of small spherical drop. The average particle size was 32.43 nm and the Zeta potential was -3.41 mV. The polysaccharides and triterpenes microemulsions showed an inhibition rate of 37.66% (57.25 mg x kg(-1) x d(-1)) and 52.34% (114.5 mg x kg(-1) x d(-1)) respectively against Heps tumor growth.

CONCLUSIONThe acquired microemulsion with small particle size is stable. It significantly inhibits the tumor growth in Heps mice.

Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Emulsions ; Female ; Liver Neoplasms, Experimental ; drug therapy ; Male ; Mice ; Neoplasm Transplantation ; Particle Size ; Polysaccharides ; therapeutic use ; Reishi ; chemistry ; Triterpenes ; therapeutic use