NONO对前列腺癌脂质代谢影响及指导他汀类药物对前列腺癌的个体化治疗的研究

The occurrence of prostate cancer combined with lipid metabolism pathway activation, its progress involved lipid metabolism restructure, so theresearchers tried to use statins in the treatment of prostate cancer, but clinical study has found that statins is not a "wide spectrum" anticancer drugsfor prostate cancer, so how to apply the reasonable individualized treatment for prostate cancer is a prominent problem.Previous studies have found that statins play the roles of anti-cancer depending on the NONO protein expression, NONO interact with SREBP1 to regulate lipid metabolism, NONO as a cofactor SREBP1 transcription factors regulates lipid metabolism, thus statins in addition to directly inhibit the activity of this enzyme existing at the same time, through the NONO/SREBP1 signal axis can play a comprehensive regulation of cholesterolsynthesis and intake.So we assume NONO molecular markers directing statins individualized application in prostate cancer, its mechanism is as a cofactor SREBP1 comprehensively regulate cholesterol metabolism pathways activity, on the basis of explorating these theories ,research focuses on applicating 11 c acetate metabolism imaging and NONO function analysis to guide the statins individualized treatment for prostate cancer.

前列腺癌的发生伴随着脂质代谢通路的活化，其进展又涉及脂质代谢通路的重组，因此研究者试图将他汀类降脂药应用于前列腺癌的治疗，然而临床研究发现他汀类药物并非前列腺癌的“广谱”抗癌药物，因此如何将之合理应用于前列腺癌的个体化治疗是个突出问题。前期研究发现他汀对前列腺癌的杀伤作用依赖于NONO蛋白的表达，NONO通过蛋白间相互作用调控脂质代谢关键因子SREBP1的活性，NONO作为SREBP1转录因子的辅助因子调节脂质代谢，因此他汀类药物除了直接抑制现有HMGCR活性的同时，通过NONO/SREBP1信号轴可以发挥对胆固醇合成和摄取的综合性调控。故研究假设NONO是指导他汀类药物在前列腺癌个体化应用分子标志物，其机制是作为SREBP1的辅助因子综合调控细胞胆固醇代谢通路活性，研究拟在探索上述理论的基础上应用11C乙酸代谢显像和NONO功能分析指导他汀类药物对前列腺癌的个体化治疗。

研究发现他汀对前列腺癌的杀伤作用依赖于NONO蛋白的表达，NONO通过蛋白间相互作用调控脂质代谢关键因子SREBP1的活性，NONO作为SREBP1转录因子的辅助因子调节脂质代谢，因此他汀类药物除了直接抑制现有HMGCR活性的同时，通过NONO/SREBP1信号轴可以发挥对胆固醇合成和摄取的综合性调控。故研究NONO是指导他汀类药物在前列腺癌个体化应用分子标志物，其机制是作为SREBP1的辅助因子综合调控细胞胆固醇代谢通路活性，研究探索上述理论的基础上应用68ga-psma显像和NONO功能分析指导他汀类药物对前列腺癌的个体化治疗。