Dataset Information

CD40 is Positively Correlated with the Expression of Nucleophosmin in Cisplatin-Resistant Bladder Cancer.

ABSTRACT: Objective:To verify and evaluate the value of CD40 as a noninvasive biomarker of cisplatin-resistant bladder cancer, we studied the expression of CD40 and the correlation between nucleophosmin (NPM1) and CD40 in cisplatin-resistant bladder cancer. Methods:Three cisplatin-resistant bladder cancer cell lines (T24/0.8DDP, BIU87/0.3DDP, and PUMC-91/0.6DDP) were studied, and lentivirus was used to silence NPM1 expression. The expression of CD40 and NPM1 in three NPM1 silencing bladder cancer cell lines were detected by fluorescence microscopy and Western Blot. The effects and proteomic bioinformatics of NPM1 gene knockout on cisplatin-resistant bladder cancer cells were analyzed by liquid chromatography-mass spectrometry (LC-MS) and gene ontology analysis (GO analysis). Results:The NPM1 gene was successfully silenced in three drug-resistant bladder cancer cell lines by lentivirus infection. The knockdown efficiency was 70%. After NPM1 gene knockout, 492 differential proteins were detected by LC-MS, whose fold change was more than 1.5 (p < 0.05). A total of 57022 peptides, 54347 unique peptides, and 6686 protein groups were identified in all proteins of the tested cells (FDR?

SUBMITTER: Luo C

PROVIDER: S-EPMC7204159 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD40 is Positively Correlated with the Expression of Nucleophosmin in Cisplatin-Resistant Bladder Cancer.

Luo Chenshuo C Lei Ting T Zhao Man M Meng Qian Q Zhang Man M

Journal of oncology 20200428

<h4>Objective</h4>To verify and evaluate the value of CD40 as a noninvasive biomarker of cisplatin-resistant bladder cancer, we studied the expression of CD40 and the correlation between nucleophosmin (NPM1) and CD40 in cisplatin-resistant bladder cancer.<h4>Methods</h4>Three cisplatin-resistant bladder cancer cell lines (T24/0.8DDP, BIU87/0.3DDP, and PUMC-91/0.6DDP) were studied, and lentivirus was used to silence NPM1 expression. The expression of CD40 and NPM1 in three NPM1 silencing bladder ...[more]

PMID: 32411234

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Project description:ObjectiveRedox adaptation plays a critical role in cancer cells' drug tolerance and sensitivity. The antioxidative response is induced by nuclear factor erythroid 2-related factor 2 (Nrf2), which triggers the transcriptional activation of genes related to chemosensitivity, glutathione synthesis, and cell protection. Although Nestin1 is known to regulate cellular redox homeostasis by regulating Nrf2 in lung cancer cells, its regulatory effect on the antioxidative state of bladder cancer (BC) cells remains unclear.MethodsThe oxidative stress levels in two cisplatin-treated BC cell lines (T24 and J82) were examined using 2',7'-dichlorofluorescin diacetate staining and real-time quantitative reverse transcription-PCR (RT-qPCR) assays. The cell viability, growth, and apoptosis were determined using CCK-8, colony formation, and flow cytometric assays, respectively. The mRNA and protein levels of Nestin1, Nrf2, and several antioxidant enzymes were quantified using RT-qPCR and western blot assays. A mouse xenograft model was used to determine the effect of Nestin1 on the T24 tumor growth in vivo.ResultsCisplatin treatment induced reactive oxygen species (ROS) generation and antioxidative damage in the T24 and J82 cells, reducing their viability and growth and triggering their apoptosis. Moreover, the Nestin1 and Nrf2 protein levels were enhanced in both treated cell lines. Loss- and gain-of-function assays indicated that Nestin1 expression was positively correlated with the Nrf2 protein expression in the BC cells. Nestin1 overexpression reduced the ROS generation, alleviated the redox disorder, promoted cell viability, and reduced apoptosis, but its silencing had the opposite effects. Importantly, Nestin1 overexpression enhanced the chemoresistance of BC cells to cisplatin in vivo, but its knockdown improved the chemosensitivity of the cells and increased their apoptosis.ConclusionThese results provide a theoretical basis for further targeting the transcription factors, including Nestin1 and Nrf2, in the treatment of BC with cisplatin.

Dataset Information

CD40 is Positively Correlated with the Expression of Nucleophosmin in Cisplatin-Resistant Bladder Cancer.

Publications

CD40 is Positively Correlated with the Expression of Nucleophosmin in Cisplatin-Resistant Bladder Cancer.

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