Intervention effect of Qi-Yu-San-Long Decoction on Lewis lung carcinoma in C57BL/6 mice: Insights from UPLC–QTOF/MS-based metabolic profiling

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1102-1103; pp. 23 - 33
• Main Authors: Wu, Huan, Chen, Yang, Li, Qinglin, Gao, Yating, Zhang, Xingxing, Tong, Jiabing, Zhang, Zhiqiang, Hu, Jian, Wang, Danyang, Zeng, Shijie, Li, Zegeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018
• Subjects: A549 Cells; Animals; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Carcinoma, Lewis Lung - metabolism; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal - pharmacology; Humans; Lipid Metabolism; Lung carcinoma; Metabolome - drug effects; Mice; Mice, Inbred C57BL; Potential biomarkers; Qi-Yu-San-Long Decoction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Untargeted metabolomics; UPLC-QTOF/MS; LLC; MVDA; PS; DMSO; SPF; UPLC-QTOF/MS; LCAT; MTT; DMEM; OD; FBS; IC50; PKC δ/ε; m/z; SM; ASM; QTOF; EIC; tR; PBS; MS; OPLS-DA; Qi-Yu-San-Long Decoction; CL; DAPI; Lung carcinoma; PCA; TIC; LysoPE; CV; LysoPC; PC; NSCLCs; UPLC; CDP-DG; PG; PI; sPLA2; cPLA2α; Potential biomarkers; QYSLD; VIP; FC; TCM; Untargeted metabolomics
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2018.10.013

Qi-Yu-San-Long Decoction (QYSLD) has been used to treat lung carcinoma for over twenty years in clinical practices, and its curative effect is considered credible. However, the therapeutic mechanism of this effect has not been thoroughly elucidated to date. In this study, a MTT dye reduction assay and DAPI staining were first used to evaluate the cell viability and apoptosis of A549 cells with and without QYSLD-treatment, respectively. The weight/volume of Lewis lung carcinoma (LLC) sarcoma was used to assess the therapeutic effect of QYSLD on LLC mice. Second, an UPLC-QTOF/MS-based untargeted metabolomics method was employed to identify and relatively quantify functional metabolites that were responsible for the intervention effect of QYSLD on LLC. As a result, the MTT dye reduction assay and DAPI staining demonstrated that QYSLD could inhibit the proliferation and induce the apoptosis of A549 cells. The weight/volume test of LLC sarcoma showed that QYSLD could restrain the development of LLC. Next, 21 potential biomarkers that could contribute to the curative mechanism of QYSLD on LLC were screened by the untargeted metabolomics method. The down-regulated metabolites induced by QYSLD included PC(16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PC(20:2(11Z,14Z)/16:0), PC(22:4(7Z,10Z,13Z,16Z)/14:0), PC(22:5(7Z,10Z,13Z,16Z,19Z)/14:0), arachidonic acid, gamma-glutamylisoleucine, cholesterol sulfate, CL (8:0/10:0/11:0/a-13:0) and CDP-DG (16:0/18:1(11Z)). The up-regulated metabolites were LysoPC(16:0), LysoPC(18:0), LysoPE(18:2(9Z,12Z)/0:0), LysoPE(22:0/0:0), LysoPE(22:1(13Z)/0:0), LysoPE(22:2(13Z,16Z)/0:0), triglylcarnitine, 1‑arachidonoylglycerophosphoinositol, 1‑palmitoylglycerophosphoinositol, 2‑stearoylglycerophosphoinositol, sphingosine 1‑phosphate(d19:1-P) and SM(d18:0/16:1(9Z)). The metabolic pathway analysis revealed that the potential biomarkers were primarily involved in glycerophospholipid metabolism, sphingolipid metabolism, steroid hormone biosynthesis, fatty acid degradation and arachidonic acid metabolism. This study demonstrated that QYSLD has a good antitumor effect and that a UPLC-QTOF/MS-based untargeted metabolomics method is a promising means of elucidating the intervention mechanism of traditional Chinese medicine formulas. [Display omitted] •A Lewis lung carcinoma (LLC) tumor-bearing mouse model was successfully established.•QYSLD was identified to have positive effects on LLC in vitro and in vivo.•Metabolomics offered a strategy to evaluate the therapeutic effects of QYSLD.•QYSLD that cure LLC were primarily linked to the regulation of lipid metabolism.•The changes in biomarkers were used to explain the underlying mechanism of QYSLD.