Planaria Regeneration as a Model to Study Hedgehog Pathway Inhibitors for Basal Cell Carcinoma

Overview

Basal cell carcinoma (BCC) is driven by abnormal activation of the Hedgehog (HH) signaling pathway through the Smoothened (SMO) receptor. HH signaling also regulates regeneration and posterior specification (polarity) in planaria (Schmidtea mediterranea). Thus, planaria may provide a low-cost in vivo model to study HH inhibitors through tissue regeneration and polarity. This planaria model was used to study HH inhibition of two HH/SMO-targeting medications relevant to BCC (vismodegib, itraconazole) as well as a skin-relevant stress/repair modulator (niacinamide). A dose-response experiment was performed to identify tolerated concentrations that still permitted regeneration. A washout experiment was done to test reversibility and identify any critical “decision windows” in regeneration. Planaria were amputated into head and tail fragments and cultured individually in 12-well plates with different medicine concentrations, with water and 0.1% DMSO controls. Outcomes included survival, regeneration markers, regeneration quality, and regeneration time. Itraconazole showed a statistically significant and sharp toxicity threshold at 1 µM. In contrast, vismodegib was tolerated through 9 µM and produced a modest, dose-dependent reduction in tail regeneration quality, consistent with impaired posterior regrowth. Niacinamide caused milder, more general dose effects at higher concentrations. A higher dose trial confirmed statistically significant mortality with vismodegib at 50 µM and niacinamide at 6000 µM. In a 24-hour washout experiment, itraconazole 0.3 µM showed statistically significant partial reversibility, suggesting an early exposure window where outcomes can improve after medication removal. These findings show that planaria can help distinguish toxicity from regeneration/polarity effects and generate testable hypotheses about HH-pathway inhibition relevant to BCC.

Competition history

• CSEF 2026 Zoology (Junior Division) · Entry J-20-13

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