AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma ce...AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.展开更多
Active targeting drug delivery systems （TDDS）, which could improve drug therapeutic efficacy and reduce toxicity, are still the focus of many scientific researches in cancer therapy. The drug circulation time and tu...Active targeting drug delivery systems （TDDS）, which could improve drug therapeutic efficacy and reduce toxicity, are still the focus of many scientific researches in cancer therapy. The drug circulation time and tumor accumulation could be significantly increased with the application of sterically stabilized liposome （SSL）. SSL could also be modified easily with certain ligands to achieve targeting drug delivery. Because many tumors overexpress somatostatin receptors （SSTRs）, octreotide （OCT） becomes a potential targeting ligand due to its high affinity to SSTRs, especially to subtype 2 （SSTR2）. In this study, OCT was conjugated to methoxypolyethyleneglycol-distearoyl-phosphatidylethanolamine （DSPE-PEG2000）, and doxorubicin （DOX）-loaded SSL with a variable percentage of octreotide-methoxypolyethyleneglycol-distearoyl-phosphatidylethanolamine （DSPE-PEG/00o-OCT） were prepared （OCT-SSL-DOX）. All liposomes were about 90 nm in diameter and negatively charged on the surface, with DOX encapsulation efficiency at above 95%. OCT modification exhibited little effect on the physicochemical properties of SSL. In this study, cellular delivery efficacy of all prepared liposomes was evaluated in SSTIL2-positive cells in vitro by flow cytometry for the optimization of the OCT density on the surface of liposomes. Lipid formulation containing 1.5% DSPE-PEG20oo-OCT exhibited the highest efficiency of intracellular drug delivery. The modification of OCT did not alter the release behaviors of liposomal DOX in vitro, but OCT-SSL-DOX increased the cytotoxicity and improved the anti-tumor effect of liposomal DOX in SST1L2- positive cells and tumor-bearing mice models. In summary, OCT-modified SSL succeeded in increasing intracellular delivery and enhancing therapeutic efficacy of encapsulated anticancer agent, suggesting that it might be a promising TDDS for the treatment of SSTR2-overexpressing cancers.展开更多
基金Supported by the Key Technologies Research and Development Program of Heilongjiang Province During the 9th Five-Year Plan Period,No.G99C 19-5
文摘AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.
基金National Basic Research Program of China(Grant No.2009CB930300)State Key Projects(Grant No.2009ZX09310-001)the 863 Project of China(Grant No.2007AA021811)
文摘Active targeting drug delivery systems （TDDS）, which could improve drug therapeutic efficacy and reduce toxicity, are still the focus of many scientific researches in cancer therapy. The drug circulation time and tumor accumulation could be significantly increased with the application of sterically stabilized liposome （SSL）. SSL could also be modified easily with certain ligands to achieve targeting drug delivery. Because many tumors overexpress somatostatin receptors （SSTRs）, octreotide （OCT） becomes a potential targeting ligand due to its high affinity to SSTRs, especially to subtype 2 （SSTR2）. In this study, OCT was conjugated to methoxypolyethyleneglycol-distearoyl-phosphatidylethanolamine （DSPE-PEG2000）, and doxorubicin （DOX）-loaded SSL with a variable percentage of octreotide-methoxypolyethyleneglycol-distearoyl-phosphatidylethanolamine （DSPE-PEG/00o-OCT） were prepared （OCT-SSL-DOX）. All liposomes were about 90 nm in diameter and negatively charged on the surface, with DOX encapsulation efficiency at above 95%. OCT modification exhibited little effect on the physicochemical properties of SSL. In this study, cellular delivery efficacy of all prepared liposomes was evaluated in SSTIL2-positive cells in vitro by flow cytometry for the optimization of the OCT density on the surface of liposomes. Lipid formulation containing 1.5% DSPE-PEG20oo-OCT exhibited the highest efficiency of intracellular drug delivery. The modification of OCT did not alter the release behaviors of liposomal DOX in vitro, but OCT-SSL-DOX increased the cytotoxicity and improved the anti-tumor effect of liposomal DOX in SST1L2- positive cells and tumor-bearing mice models. In summary, OCT-modified SSL succeeded in increasing intracellular delivery and enhancing therapeutic efficacy of encapsulated anticancer agent, suggesting that it might be a promising TDDS for the treatment of SSTR2-overexpressing cancers.
