Dataset Information

Differences in Fatty Acid Oxidation between Nab-Paclitaxel- and Solvent-Based Paclitaxel-Treated A549 Cells Based on Metabolomics.

ABSTRACT: The pharmacokinetics, safety, and anticancer efficacy profiles of nanoparticle albumin-bound (nab)-paclitaxel formulations are superior to those of solvent-based paclitaxel formulations. The aims of the present study were to study the effects of nab-paclitaxel and solvent-based paclitaxel formulations on the metabolic profiles of the model cell line (A549) and attempt to elucidate the associated metabolic pathways. A mass spectrometry-based cell metabolomics approach and viability evaluation were used to explore the potential difference. Western blotting was utilized to measure the levels of relevant proteins, and carnitine palmitoyltransferase 1 (CPT1) activities were quantified. Fold changes normalized to controls in levels of carnitine and several acylcarnitines were significantly different (p < 0.05) between A549 cells treated with nab-paclitaxel and those treated with solvent-based paclitaxel. Relative to the controls, there were also significant fold change differences in palmitic and linoleic acid levels in the cell lysates, mitochondrial CPT1 activities, and mitochondrial medium-chain acyl-CoA dehydrogenase (MCAD) protein levels in the A549 cells subjected to the nab-paclitaxel and solvent-based paclitaxel formulations. Results suggested that the two formulations differentially modulated fatty acid oxidation in the A549 cells. While cell viability results did not reveal significant differences, the findings implied that a mass spectrometry-based cell metabolomics approach could be a sensitive tool to explore the differences caused by formulation changes without using animals. Since uncertainties of products containing nanomaterials warrant holistic screening to address safety concerns, the aforementioned approach may be of regulatory importance and is worth further investigation.

SUBMITTER: Huang JW

PROVIDER: S-EPMC7931197 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Differences in Fatty Acid Oxidation between Nab-Paclitaxel- and Solvent-Based Paclitaxel-Treated A549 Cells Based on Metabolomics.

Huang Jhih-Wei JW Kuo Ching-Hua CH Kuo Han-Chun HC Shih Jin-Yuan JY Tsai Teng-Wen TW Chang Lin-Chau LC

ACS omega 20210215 8

The pharmacokinetics, safety, and anticancer efficacy profiles of nanoparticle albumin-bound (nab)-paclitaxel formulations are superior to those of solvent-based paclitaxel formulations. The aims of the present study were to study the effects of nab-paclitaxel and solvent-based paclitaxel formulations on the metabolic profiles of the model cell line (A549) and attempt to elucidate the associated metabolic pathways. A mass spectrometry-based cell metabolomics approach and viability ...[more]

PMID: 33681555

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Project description:BackgroundTo compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer.MethodsWe systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019.ResultsThe primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27-1.83, P < 0.001; ypT0/is ypN0: OR = 1.40, 95%CI: 1.17-1.68, P < 0.001). The benefits of nab-paclitaxel on pCR were persistent in HER2-negative, hormone receptor (HR)-positive breast cancer (OR = 1.53, 95%CI: 1.07-2.19, P = 0.020), triple-negative breast cancer (weekly/every 2 weeks regimen; OR = 2.95, 95%CI: 1.54-5.67, P < 0.001), and tumors with Ki-67 > 20% (OR = 1.63, 95%CI: 1.26-2.12, P < 0.001). Patients treated with nab-paclitaxel had better event-free survival (EFS; HR = 0.69, 95%CI: 0.57-0.85, P < 0.001) than with sb-taxanes. There were no differences in most of grade > 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11-0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37-3.23, P = 0.001) and grade > 3 (OR = 4.01, 95%CI: 2.51-6.41, P < 0.001) neuropathy.ConclusionNab-paclitaxel is effective for the treatment of non-metastatic breast cancer in the neoadjuvant setting. Nab-paclitaxel could improve pCR rate and EFS compared with sb-taxanes and with reasonable toxicities.

Project description:BackgroundPaclitaxel is widely used in the treatment of cancer and has a good effect in the treatment of non-small cell lung cancer. The combination of TMT proteomics and bioinformatics is used to systematically analyze the molecular mechanism of paclitaxel in the treatment of lung adenocarcinoma A549 cell, which is helpful to screen new therapeutic targets.MethodsMTT assay was used to analyze the inhibitory effect of paclitaxel on the proliferation of A549 cells. The proteins were identified by TMT quantitative proteomics and the differential expression proteins (DEPs) database was constructed. The DEPs were enriched by Gene Ontology (GO) and KEGG pathway annotation. Based on the information in the STRING database, find the interaction between DEPs, and the protein-protein interaction (PPI) networks of DEPs were constructed and analyzed by using the Cytoscape software. According to the PPI network results, select the hub proteins from DEPs for WB verification.ResultsA total of 5449 proteins were identified in A549 by TMT proteomics. Compared with the control group, 281 DEPs were significantly up-regulated and 218 were significantly down-regulated after paclitaxel treatment. GO functional analysis, we found that the main functions of these DEPs are binding, catalytic activity, molecular function regulator and so on. They are mainly involved in cellular process, metabolic process, biological regulation and so on. KEGG analysis showed that the three most significant signal transduction pathways of DEPs enrichment were DNA replication, steroid biosynthesis, oxidative phosphorylation. In PPI network, there are 294 nodes among which CDK1, MCM2-5 and PCNA are located at the center of proteins interaction. WB analysis confirmed that the expression of CDK1 was significantly down-regulated, consistent with the TMT results.ConclusionPaclitaxel significantly increased the expression of tubulin, binding tubulin to promote A549 cell death. In addition, paclitaxel significantly inhibited the expression of hub proteins, DNA replication and cell cycle pathways, thus killing lung adenocarcinoma cell A549. These findings will enhance the understanding of the mechanism of paclitaxel in the treatment of lung adenocarcinoma cell A549 and provide new valuable targets.

Dataset Information

Differences in Fatty Acid Oxidation between Nab-Paclitaxel- and Solvent-Based Paclitaxel-Treated A549 Cells Based on Metabolomics.

Publications

Differences in Fatty Acid Oxidation between <i>Nab</i>-Paclitaxel- and Solvent-Based Paclitaxel-Treated A549 Cells Based on Metabolomics.

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