卑尔根素降解生存素克服培美曲塞耐药性。

IF 4.9 2区 医学 Q2 CELL BIOLOGY
Cellular Oncology Pub Date : 2023-12-01 Epub Date: 2023-08-05 DOI:10.1007/s13402-023-00850-5
Xiaoying Li, Qi Liang, Li Zhou, Gaoyan Deng, Yeqing Xiao, Yu Gan, Shuangze Han, Jinzhuang Liao, Ruirui Wang, Xiang Qing, Wei Li
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引用次数: 0

摘要

目的:化疗耐药是导致非小细胞肺癌(NSCLC)患者治疗失败和肿瘤复发的主要因素。肿瘤蛋白survivin在人类恶性肿瘤中普遍上调,且与预后不良相关,但其在NSCLC的癌变和化疗耐药中的作用尚不明显,迫切需要探索一种针对survivin表达的有效抑制剂。方法:采用MTS法、集落形成法、免疫印迹法、免疫组化法和体内异种移植物发育法检测NSCLC细胞中survivin的肿瘤特征和卑尔根素的抗肿瘤活性。结果:Survivin在非小细胞肺癌(NSCLC)组织中表达上调,而其缺失抑制NSCLC的肿瘤发生。目前的研究主要集中在卑尔根素上,在体内和体外验证其对NSCLC细胞的有效抗肿瘤作用。结果表明,肉芽甘蓝素可通过下调survivin抑制细胞增殖,诱导细胞凋亡的内在途径。在机制上,卑尔根素通过抑制Akt/Wee1/CDK1信号通路降低survivin的磷酸化,从而增强survivin与E3连接酶fbx17的相互作用,促进survivin泛素化和降解。此外,卑尔根素促进了培美曲塞治疗再敏感的NSCLC细胞的化疗耐药。结论:Survivin过表达是维持NSCLC细胞多种恶性表型所必需的。甜菜根素通过靶向survivin对非小细胞肺癌具有较强的抗肿瘤作用,是治疗非小细胞肺癌的一种有前景的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Survivin degradation by bergenin overcomes pemetrexed resistance.

Survivin degradation by bergenin overcomes pemetrexed resistance.

Purpose: Chemoresistance is a primary factor for treatment failure and tumor recurrence in non-small cell lung cancer (NSCLC) patients. The oncoprotein survivin is commonly upregulated in human malignancies and is associated with poor prognosis, but its effect on carcinogenesis and chemoresistance in NSCLC is not yet evident, and to explore an effective inhibitor targeting survivin expression is urgently needed.

Methods: The protumor characteristics of survivin and antitumor activities of bergenin in NSCLC cells were examined by MTS, colony formation assays, immunoblot, immunohistochemistry, and in vivo xenograft development.

Results: Survivin was upregulated in non-small cell lung cancer (NSCLC) tissues, while its depletion inhibited NSCLC tumorigenesis. The current study focused on bergenin, identifying its effective antitumor effect on NSCLC cells both in vivo and in vitro. The results showed that bergenin could inhibit cell proliferation and induce the intrinsic pathway of apoptosis via downregulating survivin. Mechanistically, bergenin reduced the phosphorylation of survivin via inhibiting the Akt/Wee1/CDK1 signaling pathway, thus resulting in enhanced interaction between survivin and E3 ligase Fbxl7 to promote survivin ubiquitination and degradation. Furthermore, bergenin promoted chemoresistance in NSCLC cells re-sensitized to pemetrexed treatment.

Conclusions: Survivin overexpression is required for maintaining multiple malignant phenotypes of NSCLC cells. Bergenin exerts a potent antitumor effect on NSCLC via targeting survivin, rendering it a promising agent for the treatment of NSCLC.

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来源期刊
Cellular Oncology
Cellular Oncology ONCOLOGY-CELL BIOLOGY
CiteScore
10.30
自引率
1.50%
发文量
86
审稿时长
12 months
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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