Ni Xiaofeng, Yu Haining, Wang Shanshan, Zhang Chengcheng, Shen Shengrong
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Mar Drugs. 2017 Mar 8;15(3):66. doi: 10.3390/md15030066.
Prostate cancer (PCa), the most common malignancy in men, is a major cause of cancer deaths. A better understanding of the mechanisms that drive tumor initiation and progression may identify actionable targets to improve treatment of this patient group. As a dietary carotenoid, astaxanthin has been demonstrated to exert beneficial effects against inflammation, cardiovascular disease, oxidative damage, or different cancer sites. This study used intragastric administration of astaxanthin to detect its role on tumor proliferation, apoptosis, microRNA (miRNA) overexpression, and microbacteria composition change by establishing androgen-independent PCa cell PC-3 xenograft nude mice. Nude mice were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. The intervention was started when tumors reached 0.5-0.6 cm in diameter. Mice were intragastrically administered 100 mg/kg astaxanthin (HA), 25 mg/kg astaxanthin (LA), or olive oil (TC). The results showed that 100 mg/kg astaxanthin significantly inhibited tumor growth compared to the TC group, with an inhibitory rate of 41.7%. A decrease of Ki67 and proliferating cell nuclear antigen (PCNA) as well as an increase of cleaved caspase-3 were observed in HA-treated tumors, along with increasing apoptotic cells, obtained by TUNEL assay. The HA significantly elevated the levels of tumor suppressors miR-375 and miR-487b in tumor tissues and the amount of sp. and in mice stools, while there was no significant difference between LA and TC groups. These results provide a promising regimen to enhance the therapeutic effect in a dietary supplement manner.
前列腺癌(PCa)是男性最常见的恶性肿瘤,是癌症死亡的主要原因。更好地了解驱动肿瘤起始和进展的机制可能会确定可采取行动的靶点,以改善该患者群体的治疗。作为一种膳食类胡萝卜素,虾青素已被证明对炎症、心血管疾病、氧化损伤或不同癌症部位具有有益作用。本研究通过建立雄激素非依赖性PCa细胞PC-3异种移植裸鼠,采用胃内给药虾青素,检测其对肿瘤增殖、凋亡、微小RNA(miRNA)过表达和微生物组成变化的作用。将雄激素非依赖性前列腺癌PC-3细胞皮下接种到裸鼠体内。当肿瘤直径达到0.5 - 0.6厘米时开始干预。给小鼠胃内注射100毫克/千克虾青素(HA)、25毫克/千克虾青素(LA)或橄榄油(TC)。结果显示,与TC组相比,100毫克/千克虾青素显著抑制肿瘤生长,抑制率为41.7%。在HA处理的肿瘤中观察到Ki67和增殖细胞核抗原(PCNA)减少,以及裂解的半胱天冬酶-3增加,同时通过TUNEL检测发现凋亡细胞增加。HA显著提高了肿瘤组织中肿瘤抑制因子miR-375和miR-487b的水平以及小鼠粪便中特定菌种的数量,而LA组和TC组之间没有显著差异。这些结果提供了一种有前景的方案,以膳食补充剂的方式增强治疗效果。