2. Academic Validation
  3. Novel soluble bazedoxifene formulation gains antiproliferative and migrastatic effect in squamous cell carcinoma cells

Novel soluble bazedoxifene formulation gains antiproliferative and migrastatic effect in squamous cell carcinoma cells

  • Sci Rep. 2026 Mar 17;16(1):13743. doi: 10.1038/s41598-026-43364-4.
Lukáš Lacina 1 2 3,  Zdeněk Kejík 4 5,  Tomáš Pacák 6,  Martina Koziar Vašáková 7,  Lucie Hoznauerová 7,  Jiří Škopek 8,  Roman Ziegler 9,  Jan Brábek 9,  Jan Hajduch 1 10,  Kateřina Veselá 1 10,  Robert Kaplánek 1 10,  Pavel Martásek 10,  Karel Pacák 11,  Karel Smetana Jr 1 3,  Milan Jakubek 12 13
Affiliations

Affiliations

  • 1 First Faculty of Medicine, BIOCEV, Charles University, Průmyslová 595, 252 50, Vestec, Czech Republic.
  • 2 General University Hospital in Prague, U Nemocnice 499/2, 128 08, Prague, Czech Republic.
  • 3 First Faculty of Medicine, Institute of Anatomy, Charles University, U Nemocnice 3, 128 00, Prague, Czech Republic.
  • 4 First Faculty of Medicine, BIOCEV, Charles University, Průmyslová 595, 252 50, Vestec, Czech Republic. [email protected].
  • 5 Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08, Prague, Czech Republic. [email protected].
  • 6 Oxygen Biotech, Šafaříkova 201/17, 120 00, Prague, Czech Republic.
  • 7 Department of Respiratory Medicine, First Faculty of Medicine, Thomayer University Hospital, Charles University, Vídeňská 800, 140 59, Prague, Czech Republic.
  • 8 Clinical and Pharmacological Unit, Thomayer University Hospital, Vídeňská 800, 140 59, Prague, Czech Republic.
  • 9 Laboratory of Cancer Cell Invasion, Department of Cell Biology, Faculty of Science, BIOCEV, Charles University, Průmyslová 595, 252 50, Vestec, Czech Republic.
  • 10 Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08, Prague, Czech Republic.
  • 11 AKESO, Nárožní 1400/7, 158 00, Prague, Czech Republic.
  • 12 First Faculty of Medicine, BIOCEV, Charles University, Průmyslová 595, 252 50, Vestec, Czech Republic. [email protected].
  • 13 Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08, Prague, Czech Republic. [email protected].
PMID: 41844825 DOI: 10.1038/s41598-026-43364-4
Abstract

The IL-6 signalling pathway plays a significant role in the progression and development of squamous cell carcinoma (SCC). Bazedoxifene is a potent inhibitor of IL-6R; however, its efficacy is limited by its low solubility in water (0.54 mg/mL). In contrast, BAZE-X1, a formulation of bazedoxifene using sulfobutylether-β-cyclodextrin (SBECD), exhibits enhanced solubility (38 mg/mL). The preparation of this formulation was confirmed through X-ray diffraction and differential scanning calorimetry, while the structure of the bazedoxifene complex with SBECD was elucidated using 1D and 2D NMR spectroscopy. Although BAZE-X1 (10.0 µmol/L; 5.3 µg/mL) demonstrated no toxicity toward SCC cell lines (SCC13, LLSCC1, and FaDu), its effect on IL-6-dependent proliferation was significantly better than that of tocilizumab. The reduction in nuclear accumulation of pSTAT3 (Ser727) by BAZE-X1 was confirmed using In-Cell Western analysis. In the scratch assay, BAZE-X1, like tocilizumab, exhibited antimigratory effects against LLSCC1 but not against SCC13. However, in the context of 3D models (SCC13, LSCLC1, and FaDu), BAZE-X1 (1.0 and especially 5.0 µmol/L; 2.65 and 0.53 µg/mL) displayed a potent antimigration effect.

Keywords

Bazedoxifene; Cell colonization; Cell migration; IL-6; Squamous cell carcinoma; Sulfobutylether-β-cyclodextrin.

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