system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Apoptosis, Carcinoma, Ovarian Epithelial, Cell Line, Tumor, Cell Survival, Drug Synergism, Drug Therapy, Combination, Female, Humans, Hydroxycholesterols, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Signal Transduction, Simvastatin, Sterol Regulatory Element Binding Protein 2.
user
Do oxysterols synergize with statins by inhibiting SREBP-2 in ovarian cancer cells? Context: Determine mechanisms responsible for enhanced statin efficacy in a novel statin combination we name STOX (STatin-OXysterol). Ovarian cancer cell lines were treated with combinations of statins and oxysterols. Cell viability was determined by a modified MTT assay. Apoptosis was evaluated by immunoblotting of PARP and DAPI-mediated visualization of apoptotic nuclei. STOX effects on the expression of genes of the mevalonate pathway were assessed by real-time qPCR and immunoblotting. siRNA-mediated gene silencing was used to test the involvement of oxysterol-mediated repression of SREBP-2 in STOX synergy. The impact of statin-mediated inhibition of protein prenylation and on cholesterol homeostasis was evaluated. Oxysterols dramatically enhance cytotoxicity of statins in ovarian cancer cells through increased apoptosis. Decreased expression of SREBP-2 down-regulates the mevalonate pathway and prevents the active statin-induced sterol feedback, enhancing statin toxicity. Comparison of two ovarian cancer cell lines reveals two distinct mechanisms of statin induced toxicity, namely, dependence on protein geranylgeranylation and/or perturbation of cellular cholesterol levels.
assistant
We provide evidence of statins' mechanisms of cytotoxicity in different ovarian cancer cells and discovered a new approach to significantly enhance the anti-tumor activity of statins. These observations provide a potential new path to improve statins as a treatment against ovarian cancer with obtainable dosages. Final Decision: yes