Radiation Sensitization of Basal Cell and Head and Neck Squamous Cell Carcinoma by the Hedgehog Pathway Inhibitor Vismodegib

International Journal of Molecular Sciences
Stephanie HehlgansShahram Ghanaati

Abstract

Vismodegib, an inhibitor of the Hedgehog signaling pathway, is an approved drug for monotherapy in locally advanced or metastatic basal cell carcinoma (BCC). Data on combined modality treatment by vismodegib and radiation therapy, however, are rare. In the present study, we examined the radiation sensitizing effects of vismodegib by analyzing viability, cell cycle distribution, cell death, DNA damage repair and clonogenic survival in three-dimensional cultures of a BCC and a head and neck squamous cell carcinoma (HNSCC) cell line. We found that vismodegib decreases expression of the Hedgehog target genes glioma-associated oncogene homologue (GLI1) and the inhibitor of apoptosis protein (IAP) Survivin in a cell line- and irradiation-dependent manner, most pronounced in squamous cell carcinoma (SCC) cells. Furthermore, vismodegib significantly reduced proliferation in both cell lines, while additional irradiation only slightly further impacted on viability. Analyses of cell cycle distribution and cell death induction indicated a G1 arrest in BCC and a G2 arrest in HNSCC cells and an increased fraction of cells in SubG1 phase following combined treatment. Moreover, a significant rise in the number of phosphorylated histone-2AX/p53...Continue Reading

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Citations

Mar 25, 2020·International Ophthalmology Clinics·Davin C Ashraf, M Reza Vagefi
Jul 26, 2019·Case Reports in Orthopedics·Brianna R FramScot A Brown
Mar 3, 2020·Seminars in Cancer Biology·Jacqueline A BrinkmanStephen J Kron
Jun 9, 2020·Annales de dermatologie et de vénéréologie·R Janela-LapertM Castel

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Methods Mentioned

BETA
PCR
acetylation
Assay
flow cytometry
phase contrast microscopy

Software Mentioned

CytExpert
Office
GraphPad Prism
EXCEL
AxioVision
Image Studio Lite

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