Background and Rationale: Cancer is the second leading cause of death in the United States. Current anticancer treatments have low specificity, affecting cancerous as well as normal cells. New therapeutics approaches, such as the use of viruses with selective killing effects on cancer cells (oncolytic viruses), are worth exploring. Such an approach requires of drugs and/or procedures that would minimize infectivity to normal cells and/or enhance the virus oncolytic potency. Statins, the extensively used cholesterol-lowering drugs (i.e., Lipitor®, Zocor®) have been shown to modulate viral activity and to induce cytoprotection. More importantly, we have recently observed that the statin, simvastatin, at very low concentrations, increased the expression of the oncolytic Vesicular Stomatitis Virus (VSV), which is an attractive candidate for anticancer investigation.
Methods: In this study, we propose to expand our research activities by characterizing and comparing the effects of simvastatin on the VSV infectivity, growth and cell-killing (cytopathic actions) in cancer cells (HeLa, uterine cancer) and in UtSM (normal uterine smooth muscle) cells. Cells pretreated with different concentrations of simvastatin and subsequently infected with VSV, will be monitored for cell death and survival rates, viral replication (viral protein levels and viral titers), for cytopathic effects and for antiviral proteins.
Significance: Funding will enable us to understand the mechanisms underlying the novel viral-modulatory and cytoprotective properties of statins. Our studies will provide light on the possible role of statins as neoadjuvant and/or as modulator for future VSV oncolytic therapy.