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叶酸偶联木耳多糖-顺铂复合物对裸鼠宫颈癌的抑瘤作用。

The antitumor effect of folic acid conjugated-Auricularia auricular polysaccharide-cisplatin complex on cervical carcinoma cells in nude mice.

机构信息

Department of Food Science, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, China.

Department of Food Science, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, China.

出版信息

Int J Biol Macromol. 2018 Feb;107(Pt B):2180-2189. doi: 10.1016/j.ijbiomac.2017.10.087. Epub 2017 Nov 11.

Abstract

A tumor-targeted, folic acid (FA) conjugated-Auricularia auricular polysaccharide (AAP) -cis-diaminedichloroplatinum (CDDP) complex (FA-AAP-CDDP) was used for cervical carcinoma chemotherapy. The drug delivery system was able to enhance the antitumor potency of CDDP, and to reduce the toxic side effects of CDDP. The kidney of mice treated by FA-AAP-CDDP complex had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and lower malondialdehyde. FA-AAP-CDDP complex could induce more interleukin-2, interleukin-4, and interferon-γ in mice. In addition, the FA-AAP-CDDP complex significantly promoted the expression of Bax and caspase-3 protein, but inhibited the expression of Bcl-2 protein, which activated the mitochondrial apoptotic pathway of tumor cells in nude mice. Moreover, the FA-AAP-CDDP complex had a higher intratumoral accumulation, was lower in the kidneys. This study may provide a new direction for folate receptor targeted polymers to improve anti-tumor activity, but reduce side effects of CDDP.

摘要

一种肿瘤靶向的叶酸(FA)偶联银耳多糖(AAP)-顺二氨二氯合铂(CDDP)复合物(FA-AAP-CDDP)被用于宫颈癌的化疗。该递药系统能够增强 CDDP 的抗肿瘤效力,并降低 CDDP 的毒副作用。FA-AAP-CDDP 复合物处理的小鼠肾脏中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性更高,丙二醛含量更低。FA-AAP-CDDP 复合物能在小鼠体内诱导更多的白细胞介素-2、白细胞介素-4 和干扰素-γ。此外,FA-AAP-CDDP 复合物显著促进了 Bax 和 caspase-3 蛋白的表达,但抑制了 Bcl-2 蛋白的表达,从而激活了裸鼠肿瘤细胞的线粒体凋亡途径。此外,FA-AAP-CDDP 复合物在肿瘤组织中有更高的蓄积,肾脏中的含量更低。本研究可能为叶酸受体靶向聚合物提供了一个新的方向,以提高抗肿瘤活性,同时降低 CDDP 的副作用。

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