Translational Science 006 Contrasting exercise modes enhance muscle strength and physical function in prostate cancer survivors undertaking androgen deprivation therapy: a 12-month randomized controlled trial REBEKAH L WILSON 1 , ROBERT U NEWTON 1,2,3 , DANIEL A GALV ~ AO 1 , NIGEL SPRY 1,4,5 , FAVIL SINGH 1 , DAVID JOSEPH 1,5,6 , SUZANNE K CHAMBERS 1,7,8,9 , ROBERT A GARDINER 1,2,10 , BRAD A WALL 11 and DENNIS R TAAFFE 1 1 Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia; 2 University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia; 3 Institute of Human Performance, The University of Hong Kong, Hong Kong; 4 Genesis CancerCare, Joondalup, Western Australia, Australia; 5 Faculty of Medicine, University of Western Australia, Nedlands, Western Australia, Australia; 6 Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; 7 Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; 8 Centre for Research in Cancer Control, Cancer Council Queensland, Brisbane, Queensland, Australia; 9 Prostate Cancer Foundation of Australia, Sydney, New South Wales, Australia; 10 Department of Urology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia; 11 School of Psychology and Exercise Science, Murdoch University, Murdoch, Western Australia, Australia Objectives: Short-term supervised exercise reverses the loss of muscle strength and physical function in prostate cancer sur- vivors on androgen deprivation therapy (ADT). However, limited information exists on long-term adaptations and the prescription of different exercise modali- ties. We examined the role of contrasting 12-month exercise programmes in amelio- rating these treatment-related effects on muscle strength and physical function. Methods: 163 men (43–90 years) under- taking ADT for prostate cancer were ran- domized to: impact loading/resistance exercise (IMRT, n = 58) for 12-months supervised training; aerobic/resistance exercise (ART, n = 54) for 6-months supervised and 6-months home-based training; or delayed exercise (DEL, n = 51) 6-months usual care followed by 6-months supervised cycling exercise. Muscle strength (1RM; chest press, seated row, leg press, and leg extension) and physical function (6 m usual/fast/backward walks, chair rise, stair climb, 400 m walk, balance) were assessed at baseline, 6, and 12 months. Results: All strength tests had a signifi- cant interaction (p < 0.001) with strength generally increasing progressively in IMRT from baseline to 6 and 12 months, from baseline to 6-months in ART, and lower body strength from 6 to 12 months in DEL. There was also a significant interac- tion for repeated chair rise (p = 0.049) and a significant time effect (p < 0.001) for 400 m and all 6 m walk tests with physical function generally improving in IMRT and ART over 6 and 12 months and by 12 months in DEL. Conclusions: Different exercise modes enhance muscle strength and physical function in ADT-treated men but with highly specific adaptations. Exercise pre- scription should be tailored to ameliorate specific treatment related adverse effects. 014 PDK1 dependent aerobic glycolysis and tumorigenesis in prostate cancer is regulated by miRNAs in an allele dependent manner SUGARNIYA SUBRAMANIAM 1,2 , VARINDER JEET 1,2 , CARINA WALPOLE 1,2 , COLLEEN C NELSON 1,2 , JENNIFER H GUNTER 1,2 , JUDITH A CLEMENTS 1,2 and JYOTSNA BATRA 1,2 1 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; 2 Australian Prostate Cancer Research Centre- Queensland, Australia Objective: Genome wide association stud- ies (GWAS) recently identified single nucleotide polymorphisms (SNPs) in Pyruvate dehydrogenase kinase1 (PDK1), to be associated with prostate cancer (PCa) risk. This gene is activated under hypoxic conditions and encodes for mito- chondrial enzymes associated with meta- bolic pathways. GWAS identified two SNPs,rs1530865 (G>C) and rs2357637 (C>A), in the 3’UTR of PDK1, which were predicted to alter miRNA binding to the PDK1 gene. We hypothesised that PDK1 is involved in PCa progression by regulat- ing cellular metabolic pathways under nor- moxic and/or hypoxic conditions via miRNAs. Methods: PDK1 function in the PCa cells cells was determined using a knockdown approach and Seahorse Extracellular Flux (XF) Analyser. In addition, miRNA-SNP affinity was determined using luciferase reporter vector assay. Results: Higher expression of PDK1 was observed in PCa cell lines under hypoxic versus normoxic conditions. Under nor- moxic conditions, knockdown of PDK1 did not affect proliferation of LNCaP and PC3 cells however, the rate of migration and invasion was decreased. Furthermore, suppression of PDK1 reduced aerobic gly- colysis, in PCa cells indicating that aerobic glycolysis may promote PCa tumorigene- sis. Computational predictions revealed that PCa risk associated rs1530865 SNP was predicted to affect the binding site for miR-877-5p, miR-3125, miR-3916 and miR-3928-3p and rs2357637 for miR-889- 3p and miR-2116-3p miRNAs. Reporter gene assays confirmed that miR-3125, miR-3916 and miR-2116-3p have a speci- fic affinity for the rs1530865 SNP C-allele and rs2357637 SNP A allele respectively. Conclusions: Our findings demonstrated strong evidence for the role of miRNAs in the regulation of PDK1 in PCa in an allele dependent manner, which in turn regu- lated PCa metabolism. 021 Molecular mechanisms of metformin in prostate cancer – Mitochondrial toxicity and apoptosis H RHEE 1,2 , C NICHOLSON 1,2 , J GUNTER 1 , I VELA 1,2 and C NELSON 1 1 Australian Prostate Cancer Research Centre – Queensland, Queensland University of Technology – Institute of Health and Biomedical Innovation, Australia; 2 Department of Urology, Princess Alexandra Hospital, Australia Objectives: Metformin is a medication that may be used to counter adverse effects of ADT such as hyperinsulinaemia. Metformin has also been shown to be a potential therapeutic agent for prostate cancer. In vitro, metformin inhibits mito- chondria in prostate cancer cell lines lead- ing to apoptosis. We explored the effects of metformin in cells treated under condi- tions that mimic ADT such as hyperinsuli- naemia. © 2017 The Authors BJU International © 2017 BJU International | 120, Supplement 1, 19--23 19 Translational Science 19