Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Potential effect of MSR1 and C6-ceramide small molecules on nasopharyngeal carcinoma based on GSEA analysis

Haitao Wen¹, Guangrun Yang², Zhong Guo¹, Lixia Fan¹, Bowen Chen¹, Dapeng Zhang¹, Jiafu Zhou¹

¹Department of Otolaryngology, The Third Affiliated Hospital of Qiqihar Medical University, 27 Taishun Street, Tiefeng District, Qiqihar City, Heilongjiang Province, China; ²Department of Radiotherapy, The Third Affiliated Hospital of Qiqihar Medical University, 27 Taishun Street, Tiefeng District, Qiqihar City, Heilongjiang Province, China.

For correspondence:- Jiafu Zhou Email: zjf@qmu.edu.cn

Accepted: 2 November 2023 Published: 30 November 2023

Citation: Wen H, Yang G, Guo Z, Fan L, Chen B, Zhang D, et al. Potential effect of MSR1 and C6-ceramide small molecules on nasopharyngeal carcinoma based on GSEA analysis. Trop J Pharm Res 2023; 22(11):2287-2296 doi: 10.4314/tjpr.v22i11.7

© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate some potential therapeutic agents and targets for nasopharyngeal carcinoma (NPC).

Methods: Some potential therapeutic agents and target genes for NPC were identified by integrating bioinformatic analysis and in vitro experimental validation. Three datasets of NPC patients were gathered to reveal 26 upregulated and 344 downregulated differentially expressed genes (DGEs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analysis (KEGG) of the DGEs were implemented. Separately, 316 drug and small molecule target genes were acquired from the SEA database, allowing for detection of C6-ceramide as a small molecule of high relevance to NPC. Then, the differentially upregulated genes were intersected with potential target genes of C6-ceramide small molecules to obtain macrophage scavenger receptor 1 (MSR1). Finally, the study validated the potential roles of MSR1 and C6-ceramide in NPC cell lines.

Results: Knockdown of MSR1 expressions in NPC cells significantly decreased cell viability. Treatment with 10 μmol/L C6-ceramide also significantly reduced NPC cell viability (p < 0.0001). Furthermore, C6-ceramide attenuated the increase in MSR1 levels induced by MSR1 overexpression in NPC cells (p < 0.0001). Concurrently, MSR1 knockdown decreased expression of PI3K and AKT, while MSR1 overexpression upregulated AKT and PI3K levels.

Conclusion: MSR1 modulates viability of NPC cells by regulating PI3K and AKT expression. Additionally, C6-ceramide exerts therapeutic effect on NPC by regulating MSR1 expression. These findings reveal new therapeutic targets and strategies for the clinical management of NPC. These results establish a rationale for further exploration of MSR1 and ceramides as novel targets in NPC.

Keywords: Nasopharyngeal carcinoma, Macrophage scavenger receptor 1, C6-ceramide, PI3K/AKT pathway, Cell viability