Therapeutic role of HMG-CoA reductase inhibition in castrated Egyptian prostate cancer patients / Riham Mohamed Karkeet ; Supervised Abdelrahman N. Zekri , Ghada M. Sherif , Mohamed M. Sayed Ahmed

Thesis (Ph.D.) - Cairo University - National Cancer Institute - Department of Cancer Biology

Aim: The role of dual androgen deprivation and rosuvastatin treatment on lipid profile and lipid metabolism markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients.Methods: Of total70 castrated mPC patients, 40 patients received rosuvastatin while 30 served as control. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR) and Caveolin-1 were measured at baseline, after 3 and 6 months during the period of rosuvastatin treatment along with the measurement of patients` lipid profile (LDL, HDL, triglycerides and cholesterol) and lipid metabolism markers (aldoketoreductase (AKR1C4), HMGCoA reductase (HMGCR), ABCA1, and SLDL RP1). Patients were stratified in subgroups whose survival times were analyzed by Kaplan- Meier and COX regression for prognostic significance. Results: Before castration, HMGCR was elevated in patients <65 years (P=0.009). Bone metastasis was associated with high PSA level (P= 0.013), but low HMGCoA reductase (P= 0.004). Patients with positive family history for prostate cancer showed high levels of EGFR, triglycerides, cholesterol, LDL, alkaline phosphatase, but low AKR1C4, SLDL RP1, caveolin-1 and ABCA-1 levels. Smokers had high caveolin-1 level (P= 0.017). After 6 months of castration and rosuvastatin administration, PSA as well as triglycerides, LDL and cholesterol were significantly reduced, while AKR1C4, HMGCoA reductase, SLDL RP1, caveolin-1 and ABCA-1 were significantly increased. Overall survival (OS) was reduced in patients with high baseline SLDL RP1 >3385 pg/ml (P=0.001), high baseline PSA (>320 ng/ml) (P=0.003) and high baseline Caveoline-1>4955 pg/ml (P=0.021)

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