Inhibiting Telomerase Activity Of Liver Cancer Cell Line SMMC-7721 By Antisense HTRT

Telomerase is a specialized reverse transcriptase that is mainly composed of a protein catalytic subunit and an RNA component. The RNA subunit contain a short template sequence that directs the synthesis of DNA repeats at the ends of chromosomes. Telomerase activity, which is generally undetected in normal somatic cells, is expressed in approximately 90% tumors. Among most tumors,if telomerase were not activated tumorigenic conversion of normal human cells could not have been induced only by oncogene.More recently, expression of telomerase in conjunction with expression of simian virus 40 large T oncoprotein and an ibcigebuc allele of H-ras has been shown to promote tumorigenic conversion of normal human cells. These facts strongly support the idea that telomerase inhibition may represent a novel targeting approach for the treatment of malignant gliomas. Among the three components of telomerase (the human telomerase RNA, telomerase reverse transcriptase catalytic subunit and telomerase associated protein) hTRT is the most critical component which influences the telomerase activity. In recent years,the research for inhibiting expression of hTRT has been one of the hotspots. In this experiment ,for purpose of altering the expression of telomerase genes hTRT to induce changes in cancer cell biology and to determine its value in cancer gene therapy, the vehicle for eukaryotic expression of antisense hTRT was transfected into SMMC-7721 cells. The obtained transfectants that could produce antisense hTRT stablely showed marked decrease in telomerase activity; the shortening of telomere was obvious; contact growth inhibition of cells presented; in nude mice transplantation, the rate for tumor induction was decreased dramatically. The study also showed the antisense hTRT gene together with chemotherapeutic drugs resulted in more tumor regression in vitro than group treated with either pcl-ahTRT or chemotherapeutic drugs alone. On the whole, the results of the experiment showed that antisense expression of telomerase genes could significantly decrease cellular telomerase activity, suppress cancer cell growth and reverse malignant phenotypes .Therefore, we can conclude thataltering expression of telomerase genes may be a new pathway for cancer therapy.