This is a preprint, 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.
Research article
Shengxi Xu
Jiujiang First People's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9415-1170
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Histone deacetylase (HDAC) is closely related to the occurrence and development of breast cancer (BC). Its inhibitor (HDACi) has been used to treat BC, while the efficacy of clinical trials was not reached expectations. HDACi combined with other drugs may be an effective strategy. This study explored the effect of HDACitucidinostat combined with selinexor, anexportin 1 (XPO1) inhibitor, on BC cellsin vitro.
Methods: BC cell lines of MCF-7 (wt-TP53), MDA-MB-175 (wt-TP53), MDA-MB-134 (mut-TP53), T47D (mut-TP53) were cultured. The IC50 values of tucidinostat and selinexor on BC cells were calculated. The effects of tucidinostat and selinexor on proliferation, invasion and apoptosis of BC cells were observed accordingly. Western blotting was used to detect the protein expressions of p53, p21, Cyclin D1, Bcl-2 and Bax.
Results:Compared with mut-TP53 BC, both tucidinostat and selinexor showed better inhibitory activitiesonwt-TP53 BC including MCF-7 and MDA-MB-175. Tucidinostat combined with selinexor significantly improved the effects of tucidinostat alone on the proliferation and invasion inhibitions and apoptosis promotionsof MCF-7 and MDA-MB-175 cells in vitro. It also significantly enhanced the effects of tucidinostat on up-regulating the expression levels of acetyl-p53, nuclear p53, total p53, p21 and Bax, and down-regulating the expression levels of Cyclin D1 and Bcl-2 in MCF-7 or MDA-MB-175 cells.
Conclusion: Taken together, we believe that tucidinostat and selinexor are potentially effective drug combinations for the treatment of wt-TP53 BC, and the molecular mechanism may be throughenhancing the activity of p53 in the nucleus of BC cells to suppress proliferation and invasion and promote apoptosis of BC cells.
Keywords
HDAC, Tucidinostat, Selinexor, Breast cancer, p53
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This is a preprint, 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.
Research article
Shengxi Xu
Jiujiang First People's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9415-1170
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 27 Jul, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Histone deacetylase (HDAC) is closely related to the occurrence and development of breast cancer (BC). Its inhibitor (HDACi) has been used to treat BC, while the efficacy of clinical trials was not reached expectations. HDACi combined with other drugs may be an effective strategy. This study explored the effect of HDACitucidinostat combined with selinexor, anexportin 1 (XPO1) inhibitor, on BC cellsin vitro.
Methods: BC cell lines of MCF-7 (wt-TP53), MDA-MB-175 (wt-TP53), MDA-MB-134 (mut-TP53), T47D (mut-TP53) were cultured. The IC50 values of tucidinostat and selinexor on BC cells were calculated. The effects of tucidinostat and selinexor on proliferation, invasion and apoptosis of BC cells were observed accordingly. Western blotting was used to detect the protein expressions of p53, p21, Cyclin D1, Bcl-2 and Bax.
Results:Compared with mut-TP53 BC, both tucidinostat and selinexor showed better inhibitory activitiesonwt-TP53 BC including MCF-7 and MDA-MB-175. Tucidinostat combined with selinexor significantly improved the effects of tucidinostat alone on the proliferation and invasion inhibitions and apoptosis promotionsof MCF-7 and MDA-MB-175 cells in vitro. It also significantly enhanced the effects of tucidinostat on up-regulating the expression levels of acetyl-p53, nuclear p53, total p53, p21 and Bax, and down-regulating the expression levels of Cyclin D1 and Bcl-2 in MCF-7 or MDA-MB-175 cells.
Conclusion: Taken together, we believe that tucidinostat and selinexor are potentially effective drug combinations for the treatment of wt-TP53 BC, and the molecular mechanism may be throughenhancing the activity of p53 in the nucleus of BC cells to suppress proliferation and invasion and promote apoptosis of BC cells.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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