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

摘要

To explore the efficiency and mechanism of ovarian carcinoma gene therapy with the human fast-twitch skeletal muscle troponin I gene (Tnl-fast),Tnl-fast cDNA was transferred into human ovarian adenocarcinoma cell-line SK-OV-3.In vitro,the cell growth and cell cycle of Tnl-fast-,vector-,and mock-transfected cells were determined by MTT and flow cytometry assay,respectively.The conditioned media of Tnl-fast-,vector-,and mock-transfected SK-OV-3 cells were collected,and the cell proliferation 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 Tnl-fast were observed or analyzed,respectively.In vitro,expression of Tnl-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 Tnl-fast in the female BALB/c nude mice inhibits primary tumor growth by an average of 73%.The nude mice grafts expressing Tnl-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 angiogenesis.Our data might also provide a novel useful strategy for cancer therapy by antiangiogenic gene therapy with a specific angiogenesis inhibitor Tnl-fast.