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含槲寄生凝集素的肠溶聚合物对小鼠黑色素瘤细胞的体内外抗癌作用

Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo.

作者信息

Han Seung-Yeon, Hong Chang-Eui, Kim Hwan-Gyu, Lyu Su-Yun

机构信息

Department of Pharmacy, Sunchon National University, 255, Jungangno, Suncheon, Jeonnam, 540-742, Korea.

Department of Biology, Chonbuk National University, 567, Baekje-daero, Deokjin-gu, Jeonju-si, Jeonbuk, 561-756, Korea.

出版信息

Mol Cell Biochem. 2015 Oct;408(1-2):73-87. doi: 10.1007/s11010-015-2484-1. Epub 2015 Jul 9.

Abstract

In this study, we evaluated the effects of Korean mistletoe (Viscum album L. var. coloratum) coated with a biodegradable polymer (Eudragit(®)) wall on the growth of mouse melanoma in vivo. Oral administration of 4% (430 mg/kg/day) enteric-coated mistletoe resulted in a significant reduction in tumor volume on day 14 compared to the negative control group in B16F10 melanoma-inoculated BDF1 mice. When we measured the survival rate, enteric-coated mistletoe-received mice had a higher survival rate after day 12. Also, we investigated the mechanism involving the cancer cell growth inhibition when melanoma cells were treated with Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and its extract in vitro. As a result, a significant G0/G1 arrest was observed in both B16BL6 and B16F10 melanoma cells with VCA or mistletoe extract. In addition, VCA or mistletoe extract induced an increase in both early and late apoptosis in cells. When we studied the molecular mechanism, our results showed that VCA and mistletoe extract can increase activated multiple caspases (caspase-1, 3, 4, 5, 6, 7, 8, and 9), dose-dependently. We also found out that VCA and mistletoe treatment causes a significant decrease in the expression of procaspase-3 and 8.

摘要

在本研究中,我们评估了包裹有可生物降解聚合物(尤特奇(®))壁材的韩国槲寄生(白果槲寄生)对小鼠黑色素瘤体内生长的影响。在接种B16F10黑色素瘤的BDF1小鼠中,口服4%(430毫克/千克/天)肠溶包衣的槲寄生,与阴性对照组相比,在第14天时肿瘤体积显著减小。当我们测量存活率时,接受肠溶包衣槲寄生的小鼠在第12天后存活率更高。此外,我们研究了在体外将黑色素瘤细胞用韩国槲寄生凝集素(白果槲寄生凝集素,VCA)及其提取物处理时涉及癌细胞生长抑制的机制。结果,在B16BL6和B16F10黑色素瘤细胞中,用VCA或槲寄生提取物处理均观察到显著的G0/G1期阻滞。此外,VCA或槲寄生提取物诱导细胞早期和晚期凋亡均增加。当我们研究分子机制时,我们的结果表明,VCA和槲寄生提取物可剂量依赖性地增加多种活化的半胱天冬酶(半胱天冬酶-1、3、4、5、6、7、8和9)。我们还发现,VCA和槲寄生处理导致原半胱天冬酶-3和8的表达显著降低。

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