Endostatin in different administration routes combined with adriamycin chemotherapy in the treatment of liver cancer xenograft in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the antiangiogenetic and tumor inhibitory effects of endostatin (Es) by intratumoral versus intravenous administration combined with adriamycin (Adm) for treatment of transplanted tumor in mice.</p><p><b>METHODS</b>Forty mice were subjected to subcutaneous implantation of H22 cells and randomly divided into 4 groups by the body weight when the tumor diameter reached 1 cm, namely the control group (with intratumoral and intravenous injection of normal saline), Es intratumoral group (with intratumoral injection Es and intraperitoneal Adm injection), Es vein group (with intravenous Es injection and intraperitoneal Adm injection), and Adm group (with intratumoral saline injection and intraperitoneal Adm injection). The tumor volumes and tumor inhibition rates were calculated, and the expression of vascular endothelial growth factor (VEGF) and the microvessel density (MVD) of the tumors were examined, with the survival time of the mice also observed.</p><p><b>RESULTS</b>The tumor volume was smaller in Es intratumoral group than in the other groups (P<0.05). The expression of VEGF and M VD in Es intratumoral group was significantly decreased as compared with that in the other groups (P<0.05). The survival time was significantly longer in Es intratumoral group and Es vein group than in the other groups (P<0.05), but showed no significant difference between Es intratumoral group and Es vein group (P>0.05).</p><p><b>CONCLUSION</b>In combination with Adm regimen, Es given intratumoral injection produces better effect than intravenous Es injection against angiogenesis and tumor growth, no significant difference can be found in the survival time between them.</p>

Effect of monoclonal antibodies against LI-cadherin on the proliferation of human hepatocellular carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To obtain monoclonal antibodies (mAb) against LI-cadherin and investigate their effects on the proliferation of human hepatocellular carcinoma cells.</p><p><b>METHODS</b>Balb/c mice were immunized with recombinant LI-cadherin, and hybridoma cell lines secreting monoclonal antibodies against LI-cadherin were established with routine cell fusion and subcloning approach. The specificity of these mAbs was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of the mAbs obtained on the growth of HepG2 cells was assessed using inverted microscope and MTT assay.</p><p><b>RESULTS</b>Two hybridoma cell lines (F001 and F002) stably secreting specific mAbs were obtained. Western blot analysis showed that the two antibodies specifically recognized LI-cadherin antigen derived from human eucaryotic cells or tissue. Treatment of the HepG2 cells with the mAbs resulted in reduced viable cell number and changes in the cell morphologies, and the two mAbs inhibited the proliferation of HepG2 cells in a concentration-dependent manner (P<0.05).</p><p><b>CONCLUSION</b>The two specific mAbs obtained can inhibit the proliferation of HepG2 cells in vitro, which facilitates further study of the relationship between LI-cadherin and tumors.</p>

Effect of KDR recombinant adenovirus containing double suicide gene on the proliferation of human colon adneocarcinoma SW620 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of adenovirus (Ad)-mediated fusion gene system driven by the KDR promoter on the proliferation of human colon adenocarcinoma SW620 cells.</p><p><b>METHODS</b>The KDR-expressing SW620 cells and LS174T cells not expressing KDR were both infected with AdEasy-KDR-CDglyTK followed by treatment with the prodrugs 5-FC and/or ganciclovir at different concentrations. The effect of the transfection on the cell proliferation was evaluated.</p><p><b>RESULTS</b>The expression of green fluorescent protein (GFP) was observed in 95% of the infected SW620 and LS174T cells with a multiplicity of infection (MOI) of 100. Significant difference was not founded in the growth of SW620 and LS174T cells with or without the transfection. The infected SW620 cells exhibit high sensitivity to the prodrugs, but the infected LS174T cells did not (P<0.01). The CDglyTK fusion gene produced much stronger killing effect of on the target cells than either of the single suicide genes (P<0.01).</p><p><b>CONCLUSION</b>CDglyTK fusion gene system driven by the KDR promoter selectively kills the KDR-CDglyTK SW620 cells and inhibits the cell proliferation.</p>

Preparation of long-circulating nolatrexed dihydrochloride liposomes and its antitumor activity / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare long-circulating liposome (LCL) for sustained release of nolatrexed dihydrochloride and evaluate the effect of this preparation against the growth of hepatocarcinoma cells in mice.</p><p><b>METHODS</b>The long-circulating nolatrexed dihydrochloride liposome was prepared by film dispersion-extrusion combined with ammonium sulphate gradient method. Amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the property of the liposome membrane. The drug entrapment efficiency of the nolatrexed dihydrochloride-containing liposome was determined using UV detector with Sephadex G50. Electron microscopy and laser particle analyzer were employed to determine the size of the nolatrexed dihydrochloride liposome. For in vivo evaluation of the effect of the liposomal preparation, H22 mouse hepatoma carcinoma cells were transplanted subcutaneouly in mice in the axillary region of the right hind limb to induce growth of solid tumors, which were evaluated for tumor weight inhibition rate and tumor volume changes after administration of the LCL preparations.</p><p><b>RESULTS</b>The mean diameter of the long-circulating nolatrexed dihydrochloride liposomes was 109 nm, with an entrapment efficiency of 68.5%. In vivo antitumor experiment showed that both the common liposomal and LCL preparations of nolatrexed dihydrochloride produced antitumor effect in vivo, and the latter had weaker antitumor effect than free and common liposomal preparation of nolatrexed dihydrochloride, but in the long term, the LCL preparation showed stronger antitumor effect with a tumor weight inhibition rate of 41.68%.</p><p><b>CONCLUSION</b>LCL allows sustained release of nolatrexed dihydrochloride in vivo, and may effectively lengthen the relatively short half life of this drug after administration.</p>

Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumor-targeted drug carrier / 南方医科大学学报

<p><b>OBJECTIVE</b>To synthesize and characterize paclitaxel (PTX)-loaded folate-conjugated chitosan (FA-CTS/PTX) nanoparticles and evaluate its cytotoxicity in vitro.</p><p><b>METHODS</b>CTS/PTX and FA-CTS/PTX nanoparticles were prepared using reductive amidation and ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size was determined by laser scattering and the morphology observed using transmission electron microscopy, and the PTX content in the nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated with FA-chitosan nanoparticles in the presence or absence of folic acid in the culture medium.</p><p><b>RESULTS</b>PTX loading did not cause adhesion of the FA-CTS nanoparticles, which presented with uniform spherical morphology with an average diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater extent of intracellular uptake in the absence of folic acid, indicating that the cellular uptake of the nanoparticles occurred through endocytosis mediated by the folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX-loaded CTS nanoparticles.</p><p><b>CONCLUSION</b>FA-CTS can be a promising drug carrier with high efficiency in condensing drug, good tumor-targeting ability and low cytotoxicity.</p>