Bcl-2 expression in cell lines breast cancer and death program
Mohsen Sedaghat Janaghard1, Shahrzad Soleimani2, Abolfazl Movafagh3
1Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran. m.sharghi2001@gmail.com.
Abstract:
Breast cancer is a hormone-dependence and heterogenic disease. Drug resistance is the main reason for the failure of breast cancer treatment. Combinatory medications are methods for treatment but they are not sufficient in action. However, new approaches like molecular therapy reveal a new insight into cancer treatment. Studies show that Bcl-2 gene family inhibitors and ER blockers cause the improvement of recovery. Interfering molecules such as antisense ones can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Our team designed a new Antisense Oligonucleotide (ASO) based on Antisense oligo G3139. MCF-7 and MDA-MB-231 cell lines were used to evaluate cellular proliferation. Liposomes and cationic nano-complex (Niosome) are used to increase the cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. The results indicated significant down-regulation of the Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all cell groups. The newly designed ASO reduced the expression of the Bcl-2 gene. It also had a synergistic effect with the Tamoxifen. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 in the cancer cells.
Insights
A novel antisense oligonucleotide (ASO) targeting the Bcl-2 gene effectively inhibited breast cancer cell proliferation. This ASO, delivered via cationic nano-complexes, showed synergistic effects with Tamoxifen, offering a promising molecular therapy approach.
Area of Science:
- Oncology
- Molecular Biology
- Nanotechnology
Background:
- Breast cancer is a heterogeneous, hormone-dependent disease where drug resistance limits treatment efficacy.
- Combinatorial therapies and molecular approaches, including Bcl-2 inhibitors and ER blockers, show promise for improved recovery.
- Antisense oligonucleotides (ASOs) offer a strategy to inhibit gene expression, such as Bcl-2, potentially inducing cancer cell apoptosis.
Purpose of the Study:
- To design and evaluate a novel Antisense Oligonucleotide (ASO) based on G3139 for breast cancer treatment.
- To assess the efficacy of ASO and Tamoxifen, delivered via liposomes and cationic nano-complexes (Niosomes), in inhibiting cancer cell proliferation.
- To investigate the synergistic effects of ASO and Tamoxifen on breast cancer cells.
Main Methods:
- Design of a novel ASO targeting the Bcl-2 gene.
- Utilized MCF-7 and MDA-MB-231 breast cancer cell lines for proliferation assays.
- Employed liposomes and cationic nano-complexes (Niosomes) for enhanced cellular delivery of ASO and Tamoxifen.
- Assessed cytotoxicity and apoptosis using flow cytometry.
Main Results:
- The designed ASO significantly down-regulated Bcl-2 gene expression in breast cancer cells.
- Inhibition of MCF-7 and MDA-MB-231 cellular proliferation was observed.
- Flow cytometry confirmed early apoptosis induction across all treated cell groups.
- The ASO demonstrated a synergistic effect when combined with Tamoxifen.
Conclusions:
- The novel Bcl-2 ASO effectively reduces breast cancer cell proliferation and induces apoptosis.
- Cationic nano-complex (Niosome) delivery systems are more efficient for ASO and Tamoxifen than liposomes.
- This ASO holds potential as a targeted molecular therapy for breast cancer, especially in combination with Tamoxifen.
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