BE-64 The Effect of Long Term Exposure to Statins on Cell Proliferation and Mitochondrial Activity in Human Colorectal Cancer Cells

Colorectal cancer (CRC) is the third most common type of cancer and the third most common cause of cancer death in the United States. Over half of those diagnosed are 65 years of age or older. CRC is often treated with traditional chemotherapies, but drug resistance has been observed in other cancers due to increased expression of the ABCB1 gene after drug exposure. Therefore, it has become increasingly critical to study potential alternatives to traditional chemotherapeutics to combat this problem. One potential alternative to traditional chemotherapies is statins, a class of drugs utilized to lower levels of low-density lipoprotein, commonly known as cholesterol. Statins are HMG-CoA reductase inhibitors. HMG-CoA reductase inhibits the mevalonate pathway, which is a complex signaling pathway involved in the production of cholesterol. HMG-CoA reductase functions at the beginning of this pathway by converting acetyl-CoA to mevalonate. Mevalonate can be metabolized to a compound that has been implicated in post translational modification of GTPases Ras and Rho, which have been shown to be oncogenic. In previous studies, statins have been shown to inhibit proliferation and migration in several types of cancer. Additionally, statins are often prescribed for long durations in older adults, making this class of drug an ideal candidate for an alternative cancer treatment in this population, which is most at risk for developing CRC. For this study, CRC cell lines DLD-1 and HCT-116 were exposed to concentrations of 10 uM and 40 uM of atorvastatin and simvastatin. The positive control was 40 nM doxorubicin, and the negative control was 40 nM DMSO. Cell viability after statin exposure was assessed biweekly via the Trypan Blue Exclusion Assay and the MTS assay to determine the effectiveness of statins in decreasing cell proliferation and its possible use as an alternative to chemotherapies in treating the cancer.