Integrative Computational
Autors
Nurul Utami 1,2, Arif Setiawansyah3, Muhammad Hasan Bashari 4, Hermin Aminah Usman 5, Raden Yohana Azhar 6, Astrid Feinisa Khairani 4
Affiliations
1Doctoral Program in Medical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 2Department of Anatomy, Anatomical Pathology, and Histology, Faculty of Medicine, Universitas Lampung, Bandar Lampung, Indonesia; 3Pharmacy Diploma Program, Akademi Farmasi Cendikia Farma Husada, Bandar Lampung, Indonesia; 4Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 5Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr Hasan Sadikin General Hospital, Bandung, Indonesia; 6Division of Oncology Surgery, Department of Surgery, Faculty of Medicine, Universitas Padjadjaran/Dr Hasan Sadikin General Hospital, Bandung, Indonesia
Background
• Triple-negative breast cancer (TNBC) is aggressive and has limited targeted treatment options.
• Doxorubicin remains a cornerstone treatment, but its molecular effects beyond direct cytotoxicity are not fully understood.
Methods
• Network pharmacology analysis, molecular docking, and molecular dynamics simulations explored doxorubicin’s potential links to NF-κB and HIF-1α signaling.
• In vitro validation used MTT cytotoxicity assays in MDA-MB-231 TNBC cells, with IC50 determined and RT-qPCR measuring NF-κB and HIF-1α expression.
Key Results
• Computational analyses suggested potential associations between doxorubicin and NF-κB/HIF-1α-related pathways.
• In vitro assays showed concentration-dependent cytotoxicity, with IC50 values of 2.34 µM (DMEM) and 1.07 µM (RPMI-1640).
• RT-qPCR showed downregulation of both NF-κB and HIF-1α mRNA after doxorubicin treatment.
Discussion & Conclusion
• The findings provide transcriptional-level evidence for NF-κB- and HIF-1α-related pathway involvement in TNBC cells’ response to doxorubicin.
• Combining computational predictions with early experimental validation generates hypotheses for further mechanistic study, supporting foundational cancer research toward SDG 3.
Related SDGs
SDG 3: Good Health and Well-Being – Advancing breast cancer treatment research
Journal Information
Journal: Journal of Experimental Pharmacology
0 Comments