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大蒜提取物对膀胱癌的抗癌作用优于顺铂:通过着丝粒蛋白 M 的共同作用机制

The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M.

机构信息

* Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea.

† Department of Urology, Chungbuk National University Hospital, Cheongju, Chungbuk, South Korea.

出版信息

Am J Chin Med. 2018;46(3):689-705. doi: 10.1142/S0192415X18500362. Epub 2018 Mar 29.

Abstract

Although garlic induces apoptosis in cancer cells, it is unclear whether the effects are similar to those of cisplatin against bladder cancer (BC). Therefore, this study investigated whether garlic extracts and cisplatin show similar activity when used to treat BC. The effect of garlic on T24 BC cell line was examined in a BALB/C-nude mouse xenograft model and compared with that of cisplatin. Tissue microarray analysis and gene network analysis were performed to identify differences in gene expression by control tumors and tumors exposed to garlic extract or cisplatin. Investigation of gene expression based on tissues from 165 BC patients and normal controls was then performed to identify common targets of garlic and cisplatin. Tumor volume and tumor weight in cisplatin (0.05[Formula: see text]mg/kg)- and garlic-treated mice were significantly smaller than those in negative control mice. However, cisplatin-treated mice also showed a significant reduction in body weight. Microarray analysis of tumor tissue identified 515 common anticancer genes in the garlic and cisplatin groups ([Formula: see text]). Gene network analysis of 252 of these genes using the Cytoscape and ClueGo software packages mapped 17 genes and 9 gene ontologies to gene networks. BC (NMIBC and MIBC) patients with low expression of centromere protein M (CENPM) showed significantly better progression-free survival than those with high expression. Garlic extract shows anticancer activity in vivo similar to that of cisplatin, with no evident of side effects. Both appear to act by targeting protein-DNA complex assembly; in particular, expression of CENPM.

摘要

虽然大蒜能诱导癌细胞凋亡,但尚不清楚其作用是否与顺铂对膀胱癌(BC)的作用相似。因此,本研究旨在探讨大蒜提取物和顺铂在治疗 BC 方面是否具有相似的活性。在 BALB/C 裸鼠异种移植模型中检测了大蒜对 T24 BC 细胞系的作用,并与顺铂进行了比较。通过对对照组肿瘤和暴露于大蒜提取物或顺铂的肿瘤进行组织微阵列分析和基因网络分析,确定了基因表达的差异。对 165 例 BC 患者和正常对照组织的基因表达进行了调查,以确定大蒜和顺铂的共同靶点。顺铂(0.05[Formula: see text]mg/kg)和大蒜处理组的肿瘤体积和肿瘤重量明显小于阴性对照组。然而,顺铂处理组的小鼠体重也明显减轻。肿瘤组织的微阵列分析确定了大蒜和顺铂组中 515 个共同抗癌基因。使用 Cytoscape 和 ClueGo 软件包对这 252 个基因的基因网络进行分析,将 17 个基因和 9 个基因本体映射到基因网络中。低表达着丝粒蛋白 M(CENPM)的 BC(非肌层浸润性膀胱癌和肌层浸润性膀胱癌)患者的无进展生存期明显长于高表达者。大蒜提取物在体内具有与顺铂相似的抗癌活性,且无明显副作用。两者似乎都通过靶向蛋白质-DNA 复合物组装起作用;特别是 CENPM 的表达。

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