生物工程学报2024,Vol.40Issue(2) :529-541.DOI:10.13345/j.cjb.230443

桑根酮C通过促进β-catenin的泛素化水平抑制胶质母细胞瘤的迁移侵袭能力

Sanggenon C inhibits glioblastoma cell migration and invasion by promoting ubiquitination of β-catenin

翁雪莲 侯建兵 常洪博 崔红娟
生物工程学报2024,Vol.40Issue(2) :529-541.DOI:10.13345/j.cjb.230443

桑根酮C通过促进β-catenin的泛素化水平抑制胶质母细胞瘤的迁移侵袭能力

Sanggenon C inhibits glioblastoma cell migration and invasion by promoting ubiquitination of β-catenin

翁雪莲 1侯建兵 2常洪博 2崔红娟2
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作者信息

  • 1. 西南大学资源昆虫高效养殖与利用全国重点实验室,重庆 400716;西南大学医学研究院,重庆 400716;金凤实验室,重庆 400039;重庆市蚕丝生物材料与再生医学工程技术研究中心,重庆 400716;西南大学蚕桑纺织与生物质科学学院,重庆 400715
  • 2. 西南大学资源昆虫高效养殖与利用全国重点实验室,重庆 400716;西南大学医学研究院,重庆 400716;金凤实验室,重庆 400039;重庆市蚕丝生物材料与再生医学工程技术研究中心,重庆 400716;西南大学癌症生物医学与转化医学工程研究中心,重庆 400715
  • 折叠

摘要

胶质母细胞瘤属于浸润性的恶性肿瘤,目前其化疗新药物的寻找和治疗仍待突破.桑根酮C(Sanggenon C,SC)来源于桑白皮,在多种癌症中发挥着抗肿瘤功效.本研究利用显微镜拍摄、transwell 实验和免疫荧光实验验证了 SC 对胶质母细胞瘤的迁移侵袭能力的影响;基因富集、实时荧光定量PCR(real-time qPCR)以及泛素化实验用于阐明SC抑制胶质母细胞瘤迁移侵袭能力的分子机制.显微镜拍摄结果显示,对胶质母细胞瘤进行加药处理后细胞形态明显回缩,细胞迁移侵袭能力被削弱;Transwell实验和免疫荧光实验也验证了SC能抑制胶质母细胞瘤迁移侵袭能力的猜测;基因富集实验结果表明 SC 可能调控迁移侵袭相关基因的表达,并且影响 Wnt/β-catenin 信号通路的活性;Western blotting揭示了SC可调控β-catenin的泛素化水平,并且抑制β-catenin及其下游蛋白的表达;Real-time qPCR 实验结果在转录水平上佐证 Western blotting 的结果.SC 通过调控β-catenin的泛素化水平抑制胶质母细胞瘤的迁移侵袭能力,为胶质母细胞瘤的治疗提供了新的思路.

Abstract

Glioblastoma is a malignant and highly invasive tumor,which requires new approaches to search for chemotherapeutic agents.Sanggenon C(SC)mainly exists in the root bark of white mulberry.Although its anti-tumor effects have been reported in some cancers,the mechanism remains unclear.In this study,we used microscopic observation,transwell assay,and immunofluorescence assay to verify the effect of Sanggenon C on the migration and invasion of glioblastoma cells.We then carried out the gene set enrichment analysis(GESA),real-time qPCR assay and ubiquitination assay to delineate the molecule mechanism by which Sanggenon C affects the migration and invasion ability of glioblastoma.With the addition of Sanggenon C,glioblastoma cells were rounded up,with the migration and invasion ability weakened as verified by transwell assay and immunofluorescence assay.The results of GESA suggested that SC might regulate the expression of genes associated with migration and invasion and affect the activity of Wnt/β-catenin signaling pathway.Western blotting revealed that Sanggenon C promoted the ubiquitination of β-catenin to reduce the levels of β-catenin and its downstream proteins.This was further supported by the results of real-time qPCR analysis of target genes of β-catenin.Taken together,SC inhibits glioblastoma cell migration and invasion by enhancing β-catenin ubiquitination.Our work suggests a new direction for the treatment of glioblastoma.

关键词

胶质母细胞瘤/桑根酮C/迁移/侵袭/β-catenin泛素化

Key words

glioblastoma/Sanggenon C/migration/invasion/the ubiquitination of β-catenin

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基金项目

中央高校基本科研业务费(SWU-XDZD22006)

中央高校基本科研业务费(SWU-KT22034)

出版年

2024
生物工程学报
中国科学院微生物研究所 中国微生物学会

生物工程学报

CSTPCDCSCD北大核心
影响因子:0.641
ISSN:1000-3061
参考文献量40
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