Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma

Abstract

Feline oral squamous cell carcinomas (FOSCC) are highly aggressive neoplasms with short survival times despite multimodal treatment. FOSCC are similar to squamous cell carcinomas of the head and neck (SCCHN) in humans, which also present therapeutic challenges. The current study was undertaken to identify novel chemotherapeutics using FOSCC cell lines. A high throughput drug screen using 1,952 drugs was performed to identify chemotherapeutics for further investigation. Two of the drugs identified in the drug screen, actinomycin D and methotrexate, and two drugs with similar molecular targets to drugs found to be efficacious in the screening, dinaciclib and flavopiridol, were selected for further investigation. Drug inhibition profiles were generated for each drug and cell line using an MTS assay. In addition, the effects of the drugs of interest on cell cycle progression were analyzed via a propidium iodide DNA labeling assay. Changes in caspase-3/7 activity after treatment with each drug were also determined. The findings demonstrated effectiveness of the drugs at nanomolar concentrations with sensitivity varying across cell lines. With all of the drugs except for actinomycin D, evidence for G1 arrest was found. Dinaciclib and flavopiridol were demonstrated to induce apoptosis. The results of the study suggest that the selected drugs are potential candidates for developing novel chemotherapeutic approaches to FOSCC. Through these studies, novel therapeutic strategies for the treatment of FOSCC can be developed to provide better care for affected cats which can also serve as proof of concept studies to inform translational studies in SCCHN in humans.