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Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

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World Journal of Gastroenterology 2004年第8期10卷 1191-1197页

作者： SungYiHong MyunHeeLee WooJinHyung SungHoonNoh SeungHoChoi Kyung Sup Kim HyunCheolJung JaeKyungRoh Department of Surgery Yonsei University College of MedicineSeoulKorea Institute of Genetic Science Department of Biochemistry and Molecular BiologyYonsei University College of MedicineSeoulKorea Oncology Internal MedicineCancer Metastasis Research CenterYonsei University College of Medicine

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating ***, a sustained and high protein delivery is required to achieve the desired therapeutic *** evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell *** test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were *** biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in *** over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically *** animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated *** with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated ***,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

关键词： Adenoviridae Animals Antineoplastic Agents Antineoplastic Agents, Phytogenic Camptothecin Carcinoma, Hepatocellular Cell Line, Tumor Combined Modality Therapy DNA Topoisomerases inhibitors drug synergism Endostatins Endothelium, Vascular Enzyme Inhibitors Etoposide Gene Expression Gene Therapy Humans Liver Neoplasms Mice Research Support, Non-U.S. Gov't Sarcoma Survival Rate Umbilical Veins

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The Effect of calmodulin antagonist berbaminederivative-EBB on hepatoma in vitro and in vivo

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Chinese Medical Journal 2002年第5期115卷 759-762,157页

作者：刘杰文齐淑玲朱惠芳李卓王彤张金红中国医学科学院中国协和医科大学血液学研究所天津300020 南开大学分子生物研究所天津300071

OBJECTIVE: To evaluate the anti-hepatoma effect of Calmodulin antagonist 0 - 4-ethoxyl-butyl-Berbamine (EBB), one of the berbamine derivatives. METHODS: Monotetrazolium (MTT) method was used to analyze the effect of EBB on the proliferation and growth inhibition effect. Of a hepatoma cell line in vitro. A mouse hepatoma model was induced by injection of hepatoma cells (H22) in the abdominal cavity. The effect of EBB on survival at different concentrations as well as in combination with 5-FU were investigated in vivo. Flow cytometry analysis, dot blot hybridization, western blot, immunochemistry, enzyme-linked lectin assay (ELISA), trifluoperazine (TFP) and electron microscopic observation were used to study the effect of EBB on cell cycle process, P53 mRNA and protein levels, calmodulin content and ultrastractural changes of hepatoma cells. RESULTS: EBB exerts a very strong inhibitory effect on human hepatoma cell line 7402 and mouse hepatoma cell line H22 in vitro. The IC(50) value of EBB for the two cell lines are 3.312 microg/ml and 1.167 microg/ml, respectively. The sensitivity of H22 cells to 5-FU can be markedly enhanced: The IC(50) dosage of 5-Fu can be decreased from 0.75 microg/ml down to 0.15 microg/ml, when jointly administered with nontoxic dosages of EBB (IC(10)). In vivo, EBB can prolong the lifespan of mice with ascites H22 to more than three months. 64% of mice survived, while all animals in the control group died by the 18th day. When EBB (5 mg x kg(-1) x d(-1)) is jointly used with 5-FU (25 mg x ml(-1) x d(-1)), 73% of mice with ascites H22 survived, much higher than 27% in the 5-FU treated group. EBB can enhance the anti-hepatoma ability of 5-Fu treatment. EBB mechanism against hepatoma: P53 expression in the EBB treated group is substantially higher than that in the control group. EBB increased the translation of P53. As a calmodulin antagonist, EBB decreases amount of the CaM in hepatoma cells and blocked the hepatoma cell proliferation cycle at

关键词： Benzylisoquinolines Alkaloids Animals Antimetabolites, Antineoplastic Calmodulin Carcinoma, Hepatocellular Cell Division Cell Survival Chromatography, Thin Layer Dose-Response Relationship, drug drug synergism Fluorouracil Inhibitory Concentration 50 Liver Neoplasms, Experimental Mice Neoplasm Transplantation RNA, Messenger Research Support, Non-U.S. Gov't Tumor Cells, Cultured Tumor Suppressor Protein p53

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Synergistic action on hypnosia: Yinao capsules with pentobarbital sodium of threshold and sub-threshold dosages

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Neural Regeneration Research 2007年第2期2卷 91-94页

作者： Guilan Zhang Mingsan Miao Jingjing Shi Yalei Yang Henan College of Traditional Chinese Medicine Zhengzhou 450008 Henan Province China

BACKGROUND： Sedative and hypnotic drugs could cure insomnia in a dependent manner, and traditional Chinese medicine has some superiority in treating insomnia. OBJECTIVE： To observe the synergistic action of yinao capsules with pentobarbital sodium in threshold and sub-threshold dosages in hypnosia and sedation. DESIGN： A completely randomized grouping design and control experiment. SETTING： Pharmacological laboratory, College of Pharmacy, Henan College of Traditional Chinese Medicine. MATERIALS： Totally 200 grade II Kunming mice of 18 - 21 g, either male or female, were used. Yinao capsules, main ingredients of which were turtleback glue, thinleaf milkwort root, Chinese magnoliavine fruit, mythic fungus, tangshen, ginseng and grassleaf sweetflag rhizome, were offered by Chinese-American Huayi Pharmacy, Co.,Ltd. （ratified number： 040901）; Kangnaoshuai capsules, main ingredients of which were prepared rehmannia root, tuber fleeceflower root, ginseng, membranous milkvetch root, thinleaf milkwort root, Fushen, grassleaf sweetflag rhizome, spine date seed, lecithin, barbary wolfberry fruit, pueraria root, vitamin E, etc., were produced by Shijiazhuang Siyao, Co.,Ltd. （ratified number： 040964）; Pentobarbital sodium was produced by China Medicine （Group） Shanghai Chemical Reagent, Co,.Ltd. （Ratified number： 030816）. ZZ-6 mice spontaneous activity apparatus was produced by Chengdu Taimeng Science and Technology, Co.,Ltd. METHODS： The experiment was carried out in the Animal Experimental Center, Henan College of Traditional Chinese Medicine from October to December in 2005. （1） Influence of Yinao capsules on the spontaneous activity of mice： Fifty mice were randomly divided into five groups with 10 mice in each group： Mice in the large, middle and small dosages of Yinao capsules groups were intragastrically infused with Yinao capsules suspension （1.36, 0.68, 0.34 g/kg）; Those in the Kangnaoshuai capsules group were infused with Kangnaoshuai suspension （1.12 g/kg）; Those in t

关键词： REINFORCING AGENTS insomnia capsules pentobarbital drug synergism

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