Metabolomics study of ribavirin in the treatment of orthotopic lung cancer based on UPLC-Q-TOF/MS. (25th January 2023)

• Record Type: Journal Article
• Authors: Zhu, Shihao; Han, Xiang; Yang, Ruiying; Tian, Yizhen; Zhang, Qingqing; Wu, Yongjie; Dong, Shuhong; Zhang, Baolai
• Is Part Of: Chemico-biological interactions. Volume 370(2023)
• Publication Date: 2023-01-25
• Subjects: Ribavirin -- Metabolomics -- Metabolites -- Metabolic pathway -- Lung cancer; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.110305
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Ribavirin is a common antiviral drug, especially for patients with hepatitis C. Our recent studies demonstrated that ribavirin showed anti-tumor activity in colorectal cancer and hepatocellular carcinoma, but its effects on lung cancer remains unclear. This study aimed to evaluate the anti-tumor activity of ribavirin against lung cancer and elucidate the underlying mechanism. We established orthotopic mouse model of lung cancer (LLC and GLC-82) and employed an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach. We found that ribavirin significantly inhibited the proliferation and colony formation of lung cancer cells. Tumor sizes of orthotopic lung cancer in ribavirin-treated groups were also significantly lower than those in control groups. Metabolomics analysis revealed that ribavirin mainly affected 5 metabolic pathways in orthotopic lung tumor models, taurine and hypotaurine metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism, arginine biosynthesis and arachidonic acid metabolism. Furthermore, we identified 5 upregulated metabolites including β-nicotinamide adenine dinucleotide (NAD + ), nicotinamide (NAM), taurine, ornithine and citrulline, and 7 downregulated metabolites including 1-methylnicotinamide (MNAM), S-adenosyl-l -homocysteine (SAH), N1-Methyl-2-pyridone-5-carboxamide (2PY), homocysteine (Hcy), linoleic acid, arachidonic acid (AA) and argininosuccinic acid in ribavirin-treated groups. These results provide new insight into the anti-tumor mechanism of ribavirin for lung cancer. Highlights: Metabolomics analysis was used for antitumor effect of ribavirin on lung cancer. Ribavirin significantly inhibited growth of lung cancer cells in vitro and in vivo. Ribavirin improved five metabolic pathways in orthotopic mouse model of lung cancer. In tumors, 12 key metabolites with significant changes were identified.