title: Simvastatin Enhances the Effects of Radiotherapy and Cetuximab on a Cell Line (FaDu) Derived from a Squamous Cell Carcinoma of Head and Neck.
abstract: Radiotherapy (XRT) delivered with the antibody cetuximab is a standard treatment option for squamous cell carcinomas of head and neck (SCCNH). Cetuximab acts by blocking epidermal growth factor receptor (EGFR) signaling to inhibit cancer progression. However, a significant percentage of patients will not respond to XRT and cetuximab. Statins reduce the synthesis of cholesterol and isoprenoid derivates that may be required for efficient EGFR signaling. We assessed whether the statin simvastatin could improve this combined therapy. In vitro, simvastatin enhanced the effects of XRT alone and in combination with cetuximab in wound healing, cell proliferation, and clonogenic assays in FaDu cells. These results were reflected in xenoimplanted tumors growing into subcutaneous tissue of athymic mice where concomitant treatment with simvastatin decreased tumor growth. Consistently, lower levels of phosphorylated extracellular signal-regulated kinases 1 and 2, phosphatidylinositol 3-kinase/AKT-protein kinase B, and signal transducer and activator of transcription 3 oncoproteins and higher levels of caspase-3 and apoptosis in cell cultures and xenografts were observed. The EGFR-overexpressing A431 cell line was used to reproduce these antitumor effects of simvastatin. Our findings suggest that simvastatin may improve the efficiency of concomitant XRT and cetuximab. Further investigation in the treatment of SCCNH is warranted.
authors.affiliation: Laboratory of Translational Research, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Spain.
authors.forename: Lara I
authors.initials: LI
authors.lastname: de Llobet
authors.affiliation: Laboratory of Translational Research, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Baro
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesia
authors.affiliation: Laboratory of Translational Research, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Spain; Department of Radiation Oncology, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain. Electronic address: jbalart@santpau.cat.
authors.forename: Josep
authors.initials: J
authors.lastname: Balart