Posters

Presenting Author Academic/Professional Position

Mohammed Sikander

Academic Level (Author 1)

Faculty

Discipline/Specialty (Author 1)

Cancer and Immunology

Academic Level (Author 2)

Post-doc

Discipline/Specialty (Author 2)

Cancer and Immunology

Academic Level (Author 3)

Medical Student

Discipline/Specialty (Author 3)

Cancer and Immunology

Discipline Track

Biomedical Science

Abstract Type

Research/Clinical

Abstract

Cervical cancer (CxC) is a leading cause of mortality and morbidity among women worldwide. Current chemotherapeutic agents for CxC have shown systemic toxicity in CxC patients. Ormeloxifene (ORM) is a non-toxic and non-steroidal drug with well-defined pharmacokinetic and pharmacodynamic properties in humans. In this study, we introduce a new analogue of ormeloxifene, Bromo-ormeloxifene (Br-ORM), which demonstrates enhanced therapeutic efficacy against CxC in both in vitro and in vivo models. We investigated Br-ORM's effects on CxC cell growth through colony formation and MTS assays, alongside molecular docking studies with βcatenin using AutoDock4. Furthermore, we analyzed the influence of Br-ORM on the expression of epithelial-to-mesenchymal (EMT) markers and MMPs via Western blot and qPCR, and assessed apoptosis through Annexin-V staining. Immunofluorescence analysis highlighted the drug’s impact on β-catenin localization within cells, while the anti-tumor efficacy was evaluated in an orthotopic xenograft mouse model. Results indicated that Br-ORM notably inhibited CxC cell proliferation, decreased invasion and migration, and promoted apoptosis, along with reducing EMT-related markers and β-catenin translocation. Additionally, bioinformatics revealed a strong binding affinity of Br-ORM to β-catenin. These findings collectively suggest that Br-ORM effectively targets the β-catenin signaling pathway, thereby inhibiting CxC metastasis, indicating its potential utility as a new therapeutic alternative for treating cervical cancer.

Presentation Type

Poster

Included in

Oncology Commons

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Disruption of β-Catenin Signaling as a Strategy to Suppress EMT in Cervical Cancer

Cervical cancer (CxC) is a leading cause of mortality and morbidity among women worldwide. Current chemotherapeutic agents for CxC have shown systemic toxicity in CxC patients. Ormeloxifene (ORM) is a non-toxic and non-steroidal drug with well-defined pharmacokinetic and pharmacodynamic properties in humans. In this study, we introduce a new analogue of ormeloxifene, Bromo-ormeloxifene (Br-ORM), which demonstrates enhanced therapeutic efficacy against CxC in both in vitro and in vivo models. We investigated Br-ORM's effects on CxC cell growth through colony formation and MTS assays, alongside molecular docking studies with βcatenin using AutoDock4. Furthermore, we analyzed the influence of Br-ORM on the expression of epithelial-to-mesenchymal (EMT) markers and MMPs via Western blot and qPCR, and assessed apoptosis through Annexin-V staining. Immunofluorescence analysis highlighted the drug’s impact on β-catenin localization within cells, while the anti-tumor efficacy was evaluated in an orthotopic xenograft mouse model. Results indicated that Br-ORM notably inhibited CxC cell proliferation, decreased invasion and migration, and promoted apoptosis, along with reducing EMT-related markers and β-catenin translocation. Additionally, bioinformatics revealed a strong binding affinity of Br-ORM to β-catenin. These findings collectively suggest that Br-ORM effectively targets the β-catenin signaling pathway, thereby inhibiting CxC metastasis, indicating its potential utility as a new therapeutic alternative for treating cervical cancer.

 

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