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[Expression of antisense telomerase genes suppressing human cancer malignant phenotypes]
Objective:
Altering the expression of telomerase genes hTRT and hTR to induce changes in cancer cell biology and to determine their value in cancer gene therapy.
Methods:
By genetic transfection of antisense hTRT into HeLa cells, and treatment of PG cells with antisenes hTR oligonucleotides, their effects on cancer cell growth and malignant phenotypes were analyzed.
Results:
The vehicle for eukaryotic expression of hTRT antisense was constructed and transfected into HeLa cells. The obtained transfectants T4, T5 that could produce antisense hTRT stablely showed marked decrease in growth, with an arrest rate of 24%; the presence of contact growth inhibition was obvious; in nude mice transplantation, the rate for tumor induction was decreased from 100% to 25% or 0%; histologically, the tumor cells from inoculation of transfectant showed less nuclear chromatins and fewer giant tumor cells than those of the parent HeLa cells;the expression of PCNA was significantly reduced in the transfected cells. Treatment of antisense hTR oligonucleotides inhibited PG cell growth at a rate of 8%.
Conclusions:
Antisense expression of telomerase genes could significantly suppress cancer cell growth, decrease malignant phenotypes and histological atypia. Therefore, altering expression of telomerase genes may be a new pathway for cancer therapy.
Insights
Altering telomerase gene expression using antisense therapy significantly suppressed cancer cell growth and reduced malignant characteristics. This indicates a promising new avenue for effective cancer gene therapy strategies.
Area of Science:
- Molecular biology
- Cancer research
- Gene therapy
Context:
- Telomerase plays a crucial role in cancer cell proliferation and immortality.
- Understanding telomerase gene regulation is vital for developing targeted cancer treatments.
Purpose:
- To investigate the effects of altering human telomerase reverse transcriptase (hTRT) and human telomerase RNA (hTR) gene expression on cancer cell biology.
- To evaluate the potential of targeting telomerase genes in cancer gene therapy.
Summary:
- Antisense hTRT transfection into HeLa cells led to decreased growth (24% arrest), contact inhibition, reduced tumor formation in mice (0-25%), and less histological atypia.
- Antisense hTR oligonucleotide treatment of PG cells inhibited growth by 8%.
- Both methods demonstrated a significant reduction in proliferating cell nuclear antigen (PCNA) expression.
Impact:
- Antisense expression of telomerase genes effectively suppresses cancer cell proliferation and malignant phenotypes.
- Targeting telomerase offers a novel therapeutic strategy for cancer treatment.