Evaluating the Differential Impact of PI3 Kinase and Rock Inhibition on Carboplatin Efficacy in Ovarian Cancer Cells

For the past decade, approximately 22,000 patients have been diagnosed annually with Ovarian Cancer which has resulted in over 13,000 deaths each year. Platinum‐based chemotherapeutics such as cisplatin and carboplatin are common first line treatments for ovarian cancer. One of the major challenges with these therapies is the development of platinum resistance and disease recurrence. The phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway plays an important role in the regulation of cell survival, growth, and proliferation in ovarian cancer. Inhibition of PI3K and AKT signaling have been shown to negatively impact cell proliferation in ovarian cancer cells. Similarly, activation of the RhoA‐associated kinase (Rock) is known to enhance ovarian cancer cell migration and invasion. Here we evaluate the efficacy of specific kinase inhibitors to enhance the carboplatin induced reduction of cell proliferation in ovarian cancer cells. Cell proliferation is evaluated in SKOV‐3 cells in the presence of carboplatin alone and in combination with the PI3K inhibitor, LY294002, or the Rock inhibitor, Y27632. We hypothesize that combining carboplatin with a one of these kinase inhibitors will enhance carboplatin function thus decreasing the IC 50 and enhancing the therapeutic efficacy.