Inhibition on Telomerase Activity by Ribozyme Targeted to Human Telomerase Transcriptase

Telomerase activity is thought to be essential for continuous cell division as seen in malignant tumor cells and its inhibition could be a strategy for anti-cancer therapy. Telomerase is a ribonucleoprotein which is composed of three components called human telomerase RNA(hTR), telomerase protein 1(TP1) and human telomerase reverse transcriptase(hTERT). Among them the hTERT is the catalytic subunit and a key factor which controls the telomerase activity, so it is the best choice to inhibit telomerase through controling hTERT expression. In research two ribozymes (htert RZ and htert 5'RZ) were designed and synthesized to serve as a telomerase inhibitor. To investigate its in vivo effect of telomerase inhibition on tumor cells, these riborymes were tranfected by lipofectamine into tumor cells transiently or permenantly. Tumor cell with ribozyme genes clearly reduced the level of telomerase activities. All the transfectants with pcDNA3-htert RZ clearly grew more slowly than did the parental cell line. The doubling time of the tansfectants prolonged compared to the negative control, but no apparent apoptosis was showed although at their 37 population doublings. These findings support the potential application of these ribozymes as new theraputic agents directed against immortalized cancer cell.