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

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.