This suggest that HDV ribozyme can cleave the hTR component as hammerhead ribozyme does, but its cleaving efficacy of is higher than that of hammerhead ribozyme . Compared with L02 hepatocytes, bel 7402-RZ and HCT116-RZ cells mainly showed both Spontaneous apoptosis and blockage of cell cycle. In immortal cells, it has been shown that telomerase activity is associated with the cell cycle . The highest telomerase
activity is found in the S phase of cell cycle , whereas quiescent cells do not possess telomerase activity at a detectable level. Cancer cells escape senescence through both cell cycle checkpoint inactivation and the activation of telomerase. In addition to structural constraints, active telomerase
IKK inhibitor is one possible factor to physically shield the telomeric G-rich singlestranded overhang. The presence of free G-rich single-stranded RO4929097 cost telomeric DNA within the nucleus was found sufficient to trigger cell cycle arrest in U87 glioblastoma cells and in human fibroblasts . One might speculate that inhibition of telomerase might increase the probability that at some point in the cell cycle a free telomeric overhang becomes exposed to the nucleoplasm and could trigger cell cycle arrest or apoptosis. It was also reported that the content of telomerase RNA in cells was not parallel to the telomerase activity . In previous studies, hTR could be measured in cells, but there was no telomerase activity measured. Or, the hTR content in cells was measured high, but the telomerase activity was low. These results indicate that hTR is not the only determinant of telomerase activity.
The catalytic protein subunits are believed to be the key determinant of telomerase activity . In our northern, the uncut hTR decreased to 1/25 and 1/20 of the original in ribozyme transfected bel7402 cells and HCT116 cells respctively, while the telomerse activity Carnitine palmitoyltransferase II drop to 1/10 and 1/8 respectively of the original. The results confirm the discrepancy of telomerase activity with telomerase RNA content. Ribozyme-transfected bel7402 cells and HCT116 cells showed G1/G0 arrest and proliferation inhibition, and 75% cells showed apoptosis at 96 h. This is consistent with reduction of telomerase activity. Our results suggest that diminution of telomerase can interfere with cancer cell growth and induce cell death, presumably through apoptosis. Emerging evidence revealed that telomerase activity is associated with increased cellular resistance to apoptosis [29, 32, 33]. Telomerase activity might therefore play some role in apoptosis-controlling mechanisms and inhibition of telomerase by ribozyme might impair this pathway. Conclusion gRZ.57 we designed in the research is effective against the hTR, it is a promising agent for tumor therapy.