Dataset Information

Dual targeting of GSK3B and HDACs reduces tumor growth and improves survival in an ovarian cancer mouse model.

ABSTRACT:

Objective

To investigate the anti-tumor effect of a newly-developed dual inhibitor (APCS-540) of glycogen synthase kinase 3 beta (GSK3B) and histone deacetylases (HDACs) in ovarian cancer cells.

Methods

The effects of APCS-540 on cancer cell proliferation, migration, invasion and cancer stemness were investigated in vitro in human (KURAMOCHI, OVCA420, OVSAHO) and mouse (BR-Luc, ID8, MOSE-HRas-Myc) ovarian cancer cells. Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) cell lines were used to evaluate APCS-540's effect on chemoresistance. The immunocompetent syngeneic mouse model BR-Luc was used to test the effect of APCS-540 on ovarian cancer progression and survival.

Results

APCS-540 showed significant anti-tumor effects in vitro in both human and mouse ovarian cancer cells. Importantly, APCS-540 demonstrated marked cytotoxicity against cisplatin-resistant cancer cells and reversed cisplatin-resistance when used in combination with platinum. APCS-540 significantly decreased cancer cell invasion. A significant 66% increase in survival was observed in mice treated with APCS-540 compared to control mice.

Conclusion

Dual inhibition of GSK3B and HDACs via APCS-540 showed potent anti-tumor activity in vitro and in vivo, suggesting that APCS-540 may provide a novel treatment option for ovarian cancer, including the platinum-resistant disease.

SUBMITTER: Taylan E

PROVIDER: S-EPMC7769125 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Dual targeting of GSK3B and HDACs reduces tumor growth and improves survival in an ovarian cancer mouse model.

Taylan Enes E Zayou Fouzia F Murali Ramachandran R Karlan Beth Y BY Pandol Stephen J SJ Edderkaoui Mouad M Orsulic Sandra S

Gynecologic oncology 20200719 1

<h4>Objective</h4>To investigate the anti-tumor effect of a newly-developed dual inhibitor (APCS-540) of glycogen synthase kinase 3 beta (GSK3B) and histone deacetylases (HDACs) in ovarian cancer cells.<h4>Methods</h4>The effects of APCS-540 on cancer cell proliferation, migration, invasion and cancer stemness were investigated in vitro in human (KURAMOCHI, OVCA420, OVSAHO) and mouse (BR-Luc, ID8, MOSE-HRas-Myc) ovarian cancer cells. Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ...[more]

PMID: 32698955

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Dataset Information

Dual targeting of GSK3B and HDACs reduces tumor growth and improves survival in an ovarian cancer mouse model.

Objective

Methods

Results

Conclusion

Publications

Dual targeting of GSK3B and HDACs reduces tumor growth and improves survival in an ovarian cancer mouse model.

Similar Datasets

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