Cancer Management and Research (Aug 2021)
A Serum Metabolomic Study Reveals Changes in Metabolites During the Treatment of Lung Cancer-Bearing Mice with Anlotinib
Abstract
Xiaoting Pan,1,2,* Wenhao Chen,2,3,* Mengjun Nie,1,2 Yuanjie Liu,1,2 Zuopeng Xiao,1,2 Ying Zhang,1,2 Wei Zhang,1 Xi Zou1 1The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2No.1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 3Jiangsu Cancer Hospital, Nanjing, Jiangsu, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi ZouThe Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of ChinaTel +86-18051983568Email [email protected]: Anlotinib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor recommended for the treatment of advanced lung cancer patients after at least two previous systemic chemotherapies. Currently, many patients with lung cancer do not respond well to anlotinib treatment. Therefore, the aim of this metabolomic study was to determine the internal mechanism of anlotinib action at the molecular level and to identify the potential biomarkers and pathways associated with the therapeutic effects of anlotinib.Methods: A total of 20 male nude mice were randomly divided into 2 groups and treated with anlotinib or physiological saline. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was performed to analyze the serum samples and determine the differential metabolites and pathways between anlotinib and control groups.Results: We observed significant differences between the anlotinib and control groups, and 13 endogenous differential metabolites and 5 potential metabolic pathways were identified. Glyoxylate and dicarboxylate metabolism, tryptophan metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and valine, leucine and isoleucine biosynthesis were the most important pathways regulated by anlotinib in vivo. Notably, these 5 differential pathways were highly associated with the TCA cycle, which is important in the proliferation and apoptosis of cancer cells.Conclusion: This serum metabolomic study revealed distinct metabolic profiles in lung cancer-bearing mice treated with anlotinib and identified differential metabolites and pathways between the anlotinib and control groups, which may provide new ideas for the clinical application of anlotinib.Keywords: anlotinib, lung cancer, LC-MS, differential metabolites, pathway
