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Updated: Dec 10, 2025

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
Telomerase as a Possible Candidate Targeting Therapy in Different Breast Cancer Cell Lines
Salma Aboelela1, Abeer Ashmawy2, Sabry Shaarawy2
1Electron Microscopy Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo Egypt.
Background:
Telomerase activity is up regulated in most breast cancer subtypes but not in the adjacent normal tissues. Thus, it is a promising target for anticancer therapy. The present work investigated the effects of telomerase inhibition by siRNA on breast cancer cell lines and studied the feasibility of whether the combined effect of doxorubicin with siRNA treatment on breast cancer cells potentiates a rapid cellular response to the cytotoxic effect of chemotherapy. Methods: This study was performed on Luminal A (MCF-7), triple negative (MDA-MB-468), and HER-2/neu (SKBR-3) human breast cancer cell lines, wherein telomerase activity inhibition by hTERT siRNA and doxorubicin was detected by measuring telomerase activity using Telomeric Repeat Amplification Protocol (TRAP assay), assessing cell viability through MTT assay, and evaluating apoptosis through scanning electron microscopy (SEM) and through estimating caspase-3 and -8 activities using enzyme-linked immunosorbent assay (ELISA).
Results:
In the present study, hTERT siRNA effectively reduced telomerase activity and cell viability to more than 90% and 60%, respectively, in most breast cancer cell lines within 72 hours after transfection. The combination of hTERT siRNA and doxorubicin showed a cumulative effect compared with either treatment alone (P < 0.05). Meanwhile, SEM demonstrated apoptotic morphologic cell changes.
Conclusion:
Telomerase inhibition is a promising strategy for the effective treatment of breast cancer. When used in combination with doxorubicin, it could potentiate the cytotoxic effect of the drug on breast cancer cells.
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Insights
Telomerase inhibition using siRNA combined with doxorubicin effectively reduces breast cancer cell viability and induces apoptosis. This combination therapy shows a potentiated cytotoxic effect, offering a promising strategy for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Telomerase is upregulated in most breast cancers, making it a potential therapeutic target.
- Targeting telomerase may offer a novel approach to breast cancer treatment.
Purpose of the Study:
- To investigate the effects of telomerase inhibition by siRNA on breast cancer cell lines.
- To evaluate the combined effect of doxorubicin and siRNA treatment on breast cancer cells.
- To determine if the combination potentiates a faster cellular response to chemotherapy.
Main Methods:
- Utilized Luminal A (MCF-7), triple-negative (MDA-MB-468), and HER-2/neu (SKBR-3) human breast cancer cell lines.
- Inhibited telomerase using hTERT siRNA and treated with doxorubicin.
- Assessed telomerase activity (TRAP assay), cell viability (MTT assay), and apoptosis (SEM, Caspase-3/-8 ELISA).
Main Results:
- hTERT siRNA reduced telomerase activity (>90%) and cell viability (>60%) in most cell lines within 72 hours.
- The combination of hTERT siRNA and doxorubicin demonstrated a cumulative effect compared to monotherapy (P < 0.05).
- Scanning electron microscopy confirmed apoptotic morphological changes in treated cells.
Conclusions:
- Telomerase inhibition is a promising strategy for effective breast cancer treatment.
- Combining telomerase inhibition with doxorubicin potentiates the drug's cytotoxic effect on breast cancer cells.
- This combination approach may enhance chemotherapy efficacy in breast cancer.
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