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Expression of the human fast-twitch skeletal muscle troponin I cDNA in a human ovarian carcinoma suppresses tumor growth

查看全文 作  者:XIONG GuangWu1,3, YANG Li2, WEI YuQuan2, WANG ShiLang1, TIAN Ling2, LEI Song2, KAN Bing2 & MAO YongQiu2 1 Department of Obstetrics and Gynecology, Second Huaxi Hospital, Sichuan University, Chengdu 610041, China;2 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China;3 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100083, China 高影响力作者 出  处:《Science China(Life Sciences)》索引2007年第50卷第1期,共8页高影响力期刊 摘  要:To explore the efficiency and mechanism of ovarian carcinoma gene therapy with the human fast-twitch skeletal muscle troponin I gene (TnI-fast), TnI-fast cDNA was transferred into human ovarian adeno-carcinoma cell-line SK-OV-3. In vitro, the cell growth and cell cycle of TnI-fast-, vector-, and mock-transfected cells were determined by MTT and flow cytometry assay, respectively. The condi-tioned media of TnI-fast-, vector-, and mock-transfected SK-OV-3 cells were collected, and the cell pro-liferation inhibiting rates of human umbilical cord venous endothelial cells (HUVECs) by the three conditioned media were assayed. All the three cell lines were implanted into node mice, and the tumor growth, cell apoptosis, angiogenesis, and expression of TnI-fast were observed or analyzed, respec-tively. In vitro, expression of TnI-fast protein had no inhibiting effect on the growth of the dominant and stable transfectant cells, but endothelium, when compared with vector-transfected cells and nontrans-fected parental SK-OV-3 cells. Implantation of stable clone expressing TnI-fast in the female BALB/c nude mice inhibits primary tumor growth by an average of 73%. The nude mice grafts expressing TnI-fast exhibit a significant decrease of microvascular density, a higher rate of tumor cells apoptosis and a comparable proliferation rate as control. Our study, to our knowledge, shows the slowed down growth of the primary ovarian carcinoma, suggested that grafts were self-inhibitory by halting angio-genesis. Our data might also provide a novel useful strategy for cancer therapy by antiangiogenic gene therapy with a specific angiogenesis inhibitor TnI-fast. 关 键 词:angiogenesis gene therapy TnI-fast OVARIAN carcinoma
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