Effects Of HTERT RNAi On TRAIL-induced Apoptosis Of Gastrointestinal Malignant Tumor Cells

[Objective] TNFαand Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application for cancer therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the superfamily of tumor necrosis factor and has recently been shown to induce apoptosis in virus-infected, transformed and malignant cells, but not in normal cells. Repeated intravenous injections of TRAIL in nonhuman primates did not cause detectable toxicity to the examined tissues and organs. Moreover, TRAIL cooperated synergistically with the chemotherapy and radiotherapy causing substantial tumor regression or complete tumor ablation. Recently, it is undergoing phase I/II clinical trails. TRAIL exerted cytostatic or cytotoxic effects on the majority of tumor cell lines in vitro, however minority of them is resistant and their proliferation is further promoted by TRAIL.Apart from relation to inhibition apoptosis, repair genomic DNA injury and resistance to apoptosis inducted by chemotherapy, the main function of enzyme telomerase is to resolve end replication problem of telomeric DNA. Sensitivity of tumor cells to chemotherapy and radiotherapy will be significantly increased after the decrease of telomerase activity and shorting telomeric length.From resent researchs, we draw a conclusion that selectivity of tumor cell apoptosis induced by TRAIL may be related to the selectivity of telomerase activity expression. Sensitivity of tumor cell apoptosis induced by TRAIL may be improved because of the decreased telomerase activity.Telomerase is a RNA-dependent DNA polymerase and composes of telomerase RNA (hTR), telomerase-related protein (hTP) and telomerase reversible transcriptase (hTERT). hTERT is catalytic subunit of telomerase and plays a key role to maintain telomerase activity. Therefore, hTERT may be a new target to induce tumor cell apoptosis.Overexpression of hTERT protects acute promyelocytic leukemia (APL) cell line from TRAIL-induced apoptosis, but its molecular mechanism had not been researched further. So far, we do not know whether the resistance of TRAIL-induced tumor cell apoptosis is...