The consumption of the non-steroidal anti-inflammatory drug (NSAID) aspirin is associated with a significant reduction in the risk of developingTMPRSS2-ERG(fusion)-positive prostate cancer (PCa) compared to fusion-negative PCa in population-based case–control studies; however, no extensive preclinical studies have been conducted to investigate and confirm these protective benefits. Thus, the focus of this study was to determine the potential usefulness of aspirin and another NSAID, naproxen, in PCa prevention, employing preclinical models of bothTMPRSS2-ERG(fusion)-driven (with conditional deletion ofPten) and non-TMPRSS2-ERG-driven (Hi-Myc+/−mice) PCa. Male mice (n= 25 mice/group) were fed aspirin- (700 and 1400 ppm) and naproxen- (200 and 400 ppm) supplemented diets from (a) 6 weeks until 32 weeks of Hi-Myc+/−mice age; and (b) 1 week until 20 weeks post-Cre induction in the fusion model. In all NSAID-fed groups, compared to no-drug controls, there was a significant decrease in higher-grade adenocarcinoma incidence in theTMPRSS2-ERG(fusion)-driven PCa model. Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79–91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc+/−mice, suggesting that NSAIDs exert a specific protective effect againstTMPRSS2-ERG(fusion)-driven PCa.
基于人群的病例对照研究表明，非甾体抗炎药阿司匹林的使用与TMPRSS2-ERG（融合）阳性前列腺癌发病风险显著降低相关，而融合阴性前列腺癌则未观察到类似关联；然而，目前尚未开展深入的临床前研究以验证这些保护作用。因此，本研究旨在通过TMPRSS2-ERG（融合）驱动型（条件性敲除Pten基因）与非TMPRSS2-ERG驱动型（Hi-Myc+/-小鼠）前列腺癌临床前模型，评估阿司匹林及另一种非甾体抗炎药萘普生在预防前列腺癌中的潜在效用。雄性小鼠（每组25只）分别接受含阿司匹林（700与1400 ppm）及萘普生（200与400 ppm）的饲料干预：（a）Hi-Myc+/-小鼠组从6周龄持续喂养至32周龄；（b）融合模型组在Cre诱导后1周开始持续喂养20周。在所有非甾体抗炎药干预组中，与无药物对照组相比，TMPRSS2-ERG（融合）驱动型前列腺癌模型的高级别腺癌发生率显著降低。值得注意的是，萘普生组小鼠背外侧前列腺中未发现中分化腺癌，而阿司匹林组中分化腺癌发生率亦降低约79%-91%。相比之下，非甾体抗炎药对Hi-Myc+/-小鼠的前列腺肿瘤发生几乎未显示保护作用，这表明非甾体抗炎药对TMPRSS2-ERG（融合）驱动型前列腺癌具有特异性保护效应。
肿瘤(癌症)患者之家