Decreased AMPK promotes chemoresistance by altered lipid mediated inflammation
Ovarian cancer, the deadliest among the gynecologic cancers, poses a therapeutic challenge due to the 70% recurrence rate among patients treated with traditional chemotherapy. Novel approaches to identify chemoresistance associated markers and defining novel therapeutic strategies are in high demand for ovarian cancer treatment. My preliminary data indicated a lower AMPK level in drug-resistant ovarian cancer cells compared to its isogenic sensitive counterparts. Resistant cells are also orchestrated with increased lipid content and cytoplasmic phospholipase A2 (cPLA2) level; higher cancer stem cell (CSC) population and elevated level of cyclooxygenase 2 (COX2) enzyme. These data indicated an association between loss of AMPK to increased lipid metabolism, inflammation and stemness which could all contribute towards chemoresistance in cancer cells. Therefore, it is hypothesized that inducing AMPK and inhibiting lipid-mediated inflammatory responses in chemo resistant ovarian cancer cells will aggravate lipid degradation, reduce stemness and enhance chemosensitivity. The outcomes from this proposal will indicate whether AMPK status could be an intriguing factor to consider in ovarian cancer treatment for selecting a proper therapeutic approach. This proposal would also explore the association between AMPK to other contributing factors of chemoresistance in an in vitro and in vivo model.