Pre-Clinical Evaluation of the Tumor Suppression Effectiveness and Mechanism of Small Molecule Drugs in Oral Cancer

Integrating diseases, genes, and drugs through bioinformatics analysis could increase the efficiency of identification of potential drugs for clinical treatment. The concept is to find therapeutic candidates through comparison of the correlation between disease and drug gene signatures. Therefore, we integrated oral cancer gene signature and connectivity map drug database, and after querying, the drug shown with negative correlation may serve as therapeutic candidates to reverse oral cancer signature. Several potential small molecules with antitumor properties including natural product extracts or clinical therapeutic drugs in other diseases were identified. There is a trend to discover new application of old drugs to reduce the time and cost during drug development. Therefore, the concept of this study is to identify the therapeutic effect of potential candidate drugs. The experimental designs of this study are as follows. (1) To validate the cytotoxicity ability of candidate drugs and to examine the change of cell growth, apoptosis, and autophagy. In addition, to examine whether the candidate drugs will inhibit cell invasion ability, suppress cancer stem formation ability, and increase radio- and chemotherapy sensitivity by using cellular model. (2) To investigate the downstream effect of candidate drugs in molecular level. Drugs involved in the signaling pathway will be verified and the effect between microRNA and drug will also be examined. (3) To examine the effect of candidate drugs by in vivo animal model. We expect the results from this study may provide complete information for these drugs and improve the efficacy of therapy in oral cancer.