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Research Article
asmaa elshamy
Damanhour University Faculty of Pharmacy
Corresponding Author
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Background: Breast cancer is the most common invasive malignancy and the leading cause of tumor-related death among women globally. Excessive angiogenesis, sustained proliferation, and evasion of apoptosis are crucial for breast cancer progression. Sorafenib is a multi-kinase receptor inhibitor with anti-angiogenic activity. Stigmasterol is a phytosterol with anticancer activity. The aim of this study was to investigate molecular mechanisms of action of sorafenib and stigmasterol in two different human breast cancer cell lines and assess their combined impact on modulation of signaling pathways that control breast cancer pathogenesis.
Methods and results: MCF-7 and MDA-MB 231 cells were used as models of human breast cancer. MTT assay was used to assess cytotoxicity. Angiogenic VEGF/ VEGFR-2/ ERK/ NF-kB signaling pathway was investigated using ELISA and RT-PCR techniques. Apoptotic markers (caspase-3, Bcl2) and a proliferation marker (Ki-67) were assessed using colorimetric and ELISA techniques. Sorafenib combined with stigmasterol increased caspase-3 activity and decreased Bcl2, VEGF-A, VEGFR-2, NF-kB and Ki-67 levels.
Conclusion: The combination of Sorafenib and stigmasterol may be a useful therapeutic regimen for breast cancer treatment. This combination may inhibit angiogenesis and promote apoptosis signaling.
Keywords
Angiogenic VEGF, VEGFR-2, ERK, NF-kB, VEGFRs, DMSO
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This preprint is under consideration at Molecular Biology Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
asmaa elshamy
Damanhour University Faculty of Pharmacy
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 05 Nov, 2021
No community comments so far
Reviews received
Received 10 Nov, 2021
Reviewers invited
Invitations sent on 03 Nov, 2021
Editor assigned
On 28 Oct, 2021
First submitted
On 26 Oct, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Breast cancer is the most common invasive malignancy and the leading cause of tumor-related death among women globally. Excessive angiogenesis, sustained proliferation, and evasion of apoptosis are crucial for breast cancer progression. Sorafenib is a multi-kinase receptor inhibitor with anti-angiogenic activity. Stigmasterol is a phytosterol with anticancer activity. The aim of this study was to investigate molecular mechanisms of action of sorafenib and stigmasterol in two different human breast cancer cell lines and assess their combined impact on modulation of signaling pathways that control breast cancer pathogenesis.
Methods and results: MCF-7 and MDA-MB 231 cells were used as models of human breast cancer. MTT assay was used to assess cytotoxicity. Angiogenic VEGF/ VEGFR-2/ ERK/ NF-kB signaling pathway was investigated using ELISA and RT-PCR techniques. Apoptotic markers (caspase-3, Bcl2) and a proliferation marker (Ki-67) were assessed using colorimetric and ELISA techniques. Sorafenib combined with stigmasterol increased caspase-3 activity and decreased Bcl2, VEGF-A, VEGFR-2, NF-kB and Ki-67 levels.
Conclusion: The combination of Sorafenib and stigmasterol may be a useful therapeutic regimen for breast cancer treatment. This combination may inhibit angiogenesis and promote apoptosis signaling.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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