tailieunhanh - báo cáo khoa học: " Inhibition of telomerase activity by HDV ribozyme in cancers"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Inhibition of telomerase activity by HDV ribozyme in cancers | Journal of Experimental Clinical Cancer Research Lu et al. Journal of Experimental Clinical Cancer Research 2011 30 1 http content 30 1 1 RESEARCH Open Access Inhibition of telomerase activity by HDV ribozyme in cancers Yingying Lu1 Junchao Gu1 Dachuan Jin2 Yanjing Gao2 Mengbiao Yuan2 Abstract Background Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity. Methods A pseudo-knotted HDV ribozyme directed against the RNA component of human telomerase hTR was designed and synthesized. An in vitro transcription plasmid and a eukaryotic expression plasmid of ribozyme were constructed. The eukaryotic expression plasmid was induced into heptocellular carcinoma 7402 cells colon cancer HCT116 cells and L02 hepatocytes respectively. Then we determine the cleavage activity of ribozyme against human telomerase RNA component hTR both in vitro and in vivo and detect telomerase activity continuously. Results HDV ribozyme showed a specific cleavage activity against the telomerase RNA in vitro. The maximum cleavage ratio reached about . Transfection of HDV ribozyme into 7402 cells and colon cancer cells HCT116 led to growth arrest and the spontaneous apoptosis of cells and the telomerase activity dropped to 10 of that before. Conclussion HDV ribozyme is an effective strategy for gene therapy. Background Immortalized and malignant tumor cells are characterized by unlimited cell proliferation and programmed cell death apoptosis . It has been demonstrated that malignant transformation occurs when the telomerase in normal cell is activated 1 2 . Telomerase activity is found in almost all malignant tumors 3 . Human telomerase RNA hTR is associated with the activity of telomerase immortalized cancer cells retain the highest level of hTR 4 5 . In recent years hammerhead ribozymes were used