Abstract | 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:
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Authors | Salma Aboelela, Abeer Ashmawy, Sabry Shaarawy, Mohammed El-Hefny, Amina Medhat |
Journal | Asian Pacific journal of cancer prevention : APJCP
(Asian Pac J Cancer Prev)
Vol. 21
Issue 8
Pg. 2243-2250
(Aug 01 2020)
ISSN: 2476-762X [Electronic] Thailand |
PMID | 32856851
(Publication Type: Journal Article)
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Chemical References |
- Antibiotics, Antineoplastic
- Biomarkers, Tumor
- RNA, Small Interfering
- Doxorubicin
- TERT protein, human
- Telomerase
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Topics |
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(classification, drug therapy, metabolism, pathology)
- Cell Proliferation
- Doxorubicin
(pharmacology)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Molecular Targeted Therapy
- RNA, Small Interfering
(genetics)
- Telomerase
(antagonists & inhibitors, genetics, metabolism)
- Tumor Cells, Cultured
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