Hofseth Biocare, Kipervikgata 13, 6003 Ålesund, Norway.
GPH Biotech LLC, 1455 Adams Drive, Menlo Park, CA 94025, USA.
Mar Drugs. 2022 Mar 28;20(4):228. doi: 10.3390/md20040228.
Prostate cancer is a common cause of cancer death in men. In advanced stages of prostate cancer, androgen deprivation therapy (ADT) is initiated. Despite ADT, prostate cancers invariably progress to become androgen independent. A growing body of evidence implicates iron dysmetabolism in prostate cancer progression. A bioactive peptide-rich salmon protein hydrolysate (SPH) has previously been demonstrated to modulate iron homeostatic mechanisms. In the present study, the anticancer effect of SPH and bicalutamide co-treatment on LNCaP and PC3 prostate cancer cell proliferation was investigated. Our results found that SPH potentiates the anti-proliferative effect of bicalutamide in a dose-dependent manner for both cell lines. In the presence of 160 µg/mL SPH, co-treatment with 1.0 µM bicalutamide decreased LNCaP cells' relative colony survival from 25% (1.0 µM bicalutamide monotreatment) to 2% after culturing for 12 days. For PC3 cells, the relative colony survival diminished from 52% (10.0 µM bicalutamide) to 32% at an SPH concentration of 160 µg/mL. Gene expression profiling, employing quantitative real-time PCR, revealed that the inhibitory effects were related to significant FTH1 up-regulation with a concomitant TFRC down-regulation. In conclusion, our results provide in vitro evidence that SPH potentiates the growth inhibitory effect of bicalutamide on prostate cancer cells by modulating iron homeostasis mechanisms.
前列腺癌是男性癌症死亡的常见原因。在前列腺癌的晚期，会开始进行雄激素剥夺疗法（ADT）。尽管进行了 ADT，前列腺癌仍然不可避免地进展为雄激素非依赖性。越来越多的证据表明铁代谢失调与前列腺癌的进展有关。富含生物活性肽的三文鱼蛋白水解物（SPH）先前已被证明可以调节铁稳态机制。在本研究中，研究了 SPH 和比卡鲁胺联合治疗对 LNCaP 和 PC3 前列腺癌细胞增殖的抗癌作用。我们的研究结果发现，SPH 以剂量依赖的方式增强了比卡鲁胺对两种细胞系的抗增殖作用。在存在 160µg/mL SPH 的情况下，用 1.0µM 比卡鲁胺联合治疗会使 LNCaP 细胞的相对集落存活率从单独用 1.0µM 比卡鲁胺处理的 25%降低至 12 天后的 2%。对于 PC3 细胞，当 SPH 浓度为 160µg/mL 时，相对集落存活率从 52%（10µM 比卡鲁胺）降低至 32%。采用定量实时 PCR 的基因表达谱分析表明，抑制作用与 FTH1 的显著上调以及 TFRC 的下调有关。总之，我们的研究结果提供了体外证据，表明 SPH 通过调节铁稳态机制增强了比卡鲁胺对前列腺癌细胞的生长抑制作用。
