Back to Search
Start Over
Suppression of mTOR expression by siRNA leads to cell cycle arrest and apoptosis induction in MDA-MB-231 breast cancer cells
- Source :
- Current Gene Therapy. 23
- Publication Year :
- 2023
- Publisher :
- Bentham Science Publishers Ltd., 2023.
-
Abstract
- Background:: Mammary carcinogenesis, being ranked second in cancer-related mortality and the inadequacy of existing chemotherapy advocates the development of a novel treatment approach targeting its molecular signalling. Hyperactivation of mammalian target of rapamycin (mTOR) has a critical role in developing invasive mammary cancer and it can be a potential target. Objective:: This experiment was to explore the efficacy of mTOR-specific siRNA on therapeutic targeting of the mTOR gene, assess its proficiency in suppressing in vitro breast cancer and determine underlying molecular mechanisms. Methods:: Specific siRNA targeting mTOR was transfected into MDA-MB-231 cells and mTOR downregulation was validated through qRT-PCR and western blot analysis. Cell proliferation was analysed by MTT assay and confocal microscopy. Apoptosis was studied through flow cytometry and S6K, GSK-3β and caspase 3 expression were estimated. Further, the effect of mTOR blockade on cell cycle progression was determined. Results:: Following transfection of mTOR-siRNA into the MDA-MB-231 cells, cell viability and apoptosis were examined which indicates that clinically relevant concentration of mTOR-siRNA inhibited cell growth and proliferation and promote apoptosis, resulting from the suppression of mTOR. This leads to the downregulation of mTOR downstream S6K and upregulation of GSK-3β. An increased level of caspase 3 symbolises that the apoptotic activity is mediated through caspase-dependent pathway. Further, mTOR downregulation causes cell cycle arrest in G0/G1 phase as observed in the flow cytometry study. Conclusion:: With these results, we can conclude that mTOR-siRNA exerts direct ‘anti-breast cancer’ activity propagated by the S6K-GSK-3β- caspase 3 mediated apoptosis and by inducing cell cycle arrest. other: NA
- Subjects :
- Drug Discovery
Genetics
Molecular Medicine
Molecular Biology
Genetics (clinical)
Subjects
Details
- ISSN :
- 15665232
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Current Gene Therapy
- Accession number :
- edsair.doi...........eada84ed9132c0a9a33e8fb5f9e9058a