Analysis of metabolome changes in the HepG2 cells of apatinib treatment by using the NMR‐based metabolomics

Abstract

Neovascularization is required for the growth of tumors, vascular endothelial growth factor (VEGF) and related signal pathways are important in tumor angiogenesis. Apatinib is a highly selective and potent antiangiogenesis drug targeting the receptor of VEGFR2, blocking downstream signal transduction and inhibiting angiogenesis of tumor tissue. Apatinib has a wide range of antitumor activities in vitro and in vivo, but its effect on metabolic changes has not deeply research at present. Nowadays, our research first systematically studied the metabolic changes affected by apatinib in the HepG2 cells at the half‐maximal inhibitory concentration value. We used the metabolomics by using 1H nuclear magnetic resonance (1H‐NMR) to analyze the HepG2 cell culture media. Multivariable Statistics was applied to analyze the 1H‐NMR spectra of the cell media, including principal component analysis, partial least squares discriminant analysis (PLS‐DA) and orthogonal PLS‐DA (OPLS‐DA). Compared with the uncultured and cultured media (negative/positive control), the metabolic phenotypes were changed in the apatinib treatment with a continuous effect over time. The metabolic pathway analysis is shown that the mainly disturbed metabolic pathways pyruvate metabolism, alanine, aspartate, and glutamate metabolism and amino acid metabolism associated with them in the apatinib treatment. The differential metabolites which were identified from the reconstructed OPLS‐DA loading plots also reflected in these disturbed metabolic pathways. Our works could allow us to well understand the therapeutic effect of apatinib, especially in metabolism.

The Expectation and Reality of the HepG2 Core Metabolic Profile

“…The effect of using drugs of various natures was evaluated in 15 publications, [ 24 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Four publications studied the disturbance of the HepG2 metabolome after genetic editing [ 49 , 50 , 51 , 52 ].…”

“…Out of 56 articles, 4 had a direct link to raw data (from which one valuable dataset was kindly provided by the authors upon e-mail request [ 31 ], and three others deposited their data in a repository [ 27 , 46 , 68 ]). Twenty-three articles provided processed data in a reduced form (i.e., as complete lists of detected metabolites) [ 21 , 22 , 25 , 28 , 29 , 30 , 32 , 33 , 35 , 36 , 39 , 43 , 50 , 55 , 57 , 58 , 63 , 64 , 70 , 72 , 73 , 74 , 78 ]. The remaining 29 articles [ 23 , 24 , 37 , 38 , 40 , 41 , 42 , 44 , 45 , 47 , 48 , 49 , 51 , 52 , 53 , 54 , 56 , 59 , 60 , 61 , 62 , …”

Sterilization of black carrot juice by thermosonication: Compound changes revealed by NMR and GC–MS metabolomics methods

“…The NMR‐based metabolomics was according to the methodology by Gu et al (2019). The dried substance was dissolved in D 2 O (0.5 mL) containing TMSP.…”

Apatinib-Induced Hand–Foot Skin Reaction in Chinese Patients With Liver Cancer

“…Recently, researchers found that apatinib could also regulate the metabolic functions of liver cancer cells. For instance, Gu et al (25) reported that apatinib reduces the intake of pyruvate, and retards the secretion of lactate in HepG2 cells. According to Feng's study (26), apatinib has been demonstrated to enhance the synthesis of 3-hydroxybutyric acid (3HB), a metabolites inhibiting tumor growth both in vitro and in vivo, through activation of PPARa and promotion of fatty acid utilization.…”