The multidrug resistance can be reversed for the decrease of P-gp and LRP by inhibiting PI3K/Akt/NF-κB signal pathway in nasopharynx carcinoma

Liu, Jin; Zhu, Ming-Yi; Feng, Yun; Tang, Qianli; Xu, Meng

doi:10.1042/bsr20190239

Cited by 8 publications

(3 citation statements)

References 12 publications

(11 reference statements)

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“…As described in Table 1 , a variety of cancers, aside from CRC and PDAC, are currently treated with 5-FU, generally in combination with systemic and targeted chemotherapy, radiotherapy and/or surgery. However, for such locations, data on resistance mechanisms are even scarcer than for digestive adenocarcinomas ( 17 , 18 ). It is, therefore, crucial to improve the understanding of the mode of action of 5-FU to identify the molecular mechanisms that may be involved in long-term 5-FU based treatment failure (recurrence and metastasis) ( 19 ) and to optimize the use of 5-FU for the management of patients with advanced digestive or extra-digestive cancers.…”

Section: Introductionmentioning

confidence: 99%

A novel view on an old drug, 5-fluorouracil: an unexpected RNA modifier with intriguing impact on cancer cell fate

et al. 2021

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5-Fluorouracil (5-FU) is a chemotherapeutic drug widely used to treat patients with solid tumours, such as colorectal and pancreatic cancers. Colorectal cancer (CRC) is the second leading cause of cancer-related death and half of patients experience tumour recurrence. Used for over 60 years, 5-FU was long thought to exert its cytotoxic effects by altering DNA metabolism. However, 5-FU mode of action is more complex than previously anticipated since 5-FU is an extrinsic source of RNA modifications through its ability to be incorporated into most classes of RNA. In particular, a recent report highlighted that, by its integration into the most abundant RNA, namely ribosomal RNA (rRNA), 5-FU creates fluorinated active ribosomes and induces translational reprogramming. Here, we review the historical knowledge of 5-FU mode of action and discuss progress in the field of 5-FU-induced RNA modifications. The case of rRNA, the essential component of ribosome and translational activity, and the plasticity of which was recently associated with cancer, is highlighted. We propose that translational reprogramming, induced by 5-FU integration in ribosomes, contributes to 5-FU-driven cell plasticity and ultimately to relapse.

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Section: Introductionmentioning

confidence: 99%

A novel view on an old drug, 5-fluorouracil: an unexpected RNA modifier with intriguing impact on cancer cell fate

et al. 2021

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“…The PI3K signalling pathway is involved in MDR in various cancers. ABC membrane transporters reduce and drug resistance can be reversed following the inhibition of the PI3K signalling pathway [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Shenqi Fuzheng injection reverses M2 macrophage-mediated cisplatin resistance through the PI3K pathway in breast cancer

Yan

Shi

et al. 2023

PLoS ONE

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Background Shenqi Fuzheng injection (SQFZ) combined with chemotherapy can sensitize tumour cells. However, the mechanisms underlying SQFZ’s effects remain unknown. In human breast cancer cell lines and M2 macrophages, we showed that SQFZ was a significantly potent agent of sensitization. Methods The human breast cancer cell line, MDA-MB-231/DDP, and the human acute leukaemia mononuclear cell line, THP-1, were used. MDA-MB-231/DDP breast cancer xenografts were established to monitor tumour growth. Resistance-associated proteins were examined by western blotting. Levels of cytokines and chemokines were detected by ELISA. Cell viability was measured using the MTT assay. Apoptosis was detected by flow cytometric analysis. Results SQFZ significantly enhanced the capability of cisplatin to reduce tumour mass. SQFZ and cisplatin decreased the expression of CD206 by 1.89-fold and increased that of CD86 by 1.76-fold as compared to cisplatin alone. The levels of PGE2, IL-6, and CCL1 decreased significantly, and the activation of p-PI3K and the expressions of P-gp and ABCG2 were also inhibited by SQFZ in combination with cisplatin treatment in vivo. The survival following cisplatin administration of 60 μM and 120 μM reduced significantly in the presence of SQFZ in MDA-MB-231/DDP and M2 co-cultured cells. IGF-1, a PI3K activator, combined with SQFZ weakened the effects of SQFZ-induced apoptosis from 28.7% to 10.5%. The effects of IGF-1 on increasing the expressions of P-gp, ABCG2, and Bcl-2, and decreasing that of Bax were reversed by SQFZ. Conclusion Our findings provide evidence that SQFZ is a potential therapeutic drug for cancer therapy.

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“…Activation of this pathway can promote the proliferation of various tumor cells, including hepatocellular carcinoma, bladder cancer, and cervical carcinoma, inhibit tumor cell apoptosis, and resist sensitivity to radiotherapy and chemotherapy [41][42][43]. Liu et al demonstrated that inhibition of the PI3K/Akt/NF-κB signaling pathway reverses drug resistance in NPC [44]. Moreover, activation of the PI3K/Akt signaling pathway decreases the expression of the CDK inhibitors p21 and p27, thereby promoting cell cycle progression, which causes the proliferating cells to undergo uncontrollable proliferation by escaping from the regulation of p21 and p27, ultimately causing tumor progression [45][46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of MicroRNA-1 and Its Potential Molecular Mechanism in Nasopharyngeal Cancer: An Investigation Combined with In Silico and In-House Immunohistochemistry Validation

et al. 2022

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Background. This study was aimed at elucidating the molecular biological mechanisms of microRNA-1 (miR-1) in nasopharyngeal carcinoma (NPC). Method. In this study, we performed a pooled analysis of miR-1 expression data derived from public databases, such as GEO, ArrayExpress, TCGA, and GTEx. The miRWalk 2.0 database, combined with the mRNA microarray datasets, was used to screen the target genes, and the genes were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis using the DAVID 6.8 database. We then used the STRING 11.0 database and Cytoscape 3.80 software to construct a protein-protein interaction (PPI) network for screening hub genes. Immunohistochemistry (IHC) was further used to validate the expression of hub genes. Finally, potential therapeutic agents for NPC were screened by the Connectivity Map (cMap) database. Results. Pooled analysis showed that miR-1 expression was significantly decreased in NPC ( SMD = − 0.57 ; P < 0.05 ). The summary receiver operating characteristic curve suggested that miR-1 had a good ability to distinguish cancerous tissues from noncancerous tissues ( AUC = 0.78 ). The results of GO analysis focused on mitotic nuclear division, DNA replication, cell division, cell adhesion, extracellular space, kinesin complex, and extracellular matrix (ECM) structural constituent. The KEGG analysis suggested that the target genes played a role in key signaling pathways, such as cell cycle, focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, and PI3K/Akt signaling pathway. The PPI network suggested that cyclin-dependent kinase 1 (CDK1) was the hub gene, and the CDK1 protein was subsequently confirmed to be significantly upregulated in NPC tissues by IHC. Finally, potential therapeutic drugs, such as masitinib, were obtained by the cMap database. Conclusion. miR-1 may play a vital part in NPC tumorigenesis and progression by regulating focal adhesion kinase to participate in cell mitosis, regulating ECM degradation, and affecting the PI3K/Akt signaling pathway. miR-1 has the potential to be a therapeutic target for NPC.

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The multidrug resistance can be reversed for the decrease of P-gp and LRP by inhibiting PI3K/Akt/NF-κB signal pathway in nasopharynx carcinoma

Cited by 8 publications

References 12 publications

A novel view on an old drug, 5-fluorouracil: an unexpected RNA modifier with intriguing impact on cancer cell fate

A novel view on an old drug, 5-fluorouracil: an unexpected RNA modifier with intriguing impact on cancer cell fate

Shenqi Fuzheng injection reverses M2 macrophage-mediated cisplatin resistance through the PI3K pathway in breast cancer

Downregulation of MicroRNA-1 and Its Potential Molecular Mechanism in Nasopharyngeal Cancer: An Investigation Combined with In Silico and In-House Immunohistochemistry Validation

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