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High-dose vitamin D metabolite delivery inhibits breast cancer metastasis
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2021-10-21 , DOI: 10.1002/btm2.10263
Jiaye Liu 1, 2, 3, 4 , Junyi Shen 5 , Chunyang Mu 5 , Yang Liu 1, 2 , Dongsheng He 6 , Han Luo 1, 2 , Wenshuang Wu 1, 2 , Xun Zheng 1, 2 , Yi Liu 7 , Sunrui Chen 8 , Qiuwei Pan 9 , Yiguo Hu 3 , Yinyun Ni 4 , Yang Wang 10 , Yong Liu 11 , Zhihui Li 1, 2
Affiliation  

Besides its well-known benefits on human health, calcitriol, the hormonally active form of vitamin D3, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high-dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one-step self-assembly of calcitriol and amphiphilic cholesterol-based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors.

中文翻译:


高剂量维生素 D 代谢物递送抑制乳腺癌转移



除了众所周知的对人类健康的益处外,骨化三醇(维生素 D 3的激素活性形式)已在临床试验中作为抗癌剂进行评估。然而,目前可用的结果是矛盾的,并且没有从根本上破译。据我们所知,高剂量骨化三醇引起的高钙血症及其低生物利用度限制了其抗癌研究和转化。在这里,我们证明骨化三醇和两亲性胆固醇缀合物的一步自组装导致形成稳定的极简胶束纳米系统。当给予小鼠时,该纳米系统在乳腺肿瘤细胞中表现出高剂量的骨化三醇、显着的肿瘤生长抑制和抗转移能力以及良好的生物相容性。我们进一步揭示,潜在的分子抗转移机制涉及原发性肿瘤中促进转移的蛋白质的下调和桩蛋白(粘着斑的关键蛋白质)的上调。
更新日期:2021-10-21
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