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Choriocarcinoma (CC) is a malignant trophoblastic tumor that occurs in women of childbearing age. Its cure rate could be over 90% following single drug or multidrug chemotherapy with methotrexate, 5-fluorouracil and etc. Chemoresistance is the main cause of treatment failure in CC, and the mechanisms have yet to be elucidated. Most of the previous works on the chemoresistance of CC focused on the transcript and protein levels, and much less attention was put on the metabolic level. In this study, the metabolomic phenotypes of two lines of CC cell, methotrexate-resistant cell (JEG3R) and methotrexate-sensitive cell (JEG3), as well as the medium extracts, were investigated using an NMR-based metabonomics method. The results showed that the chemoresistance of CC was likely related to disturbed glucose metabolism. Glucitol accumulation was observed only in the JEG3R cell line, suggesting the involvement of aldose reductase in the development of chemoresistance. In addition, methotrexate chemoresistance was also associated with lactate accumulation and stimulated alanine synthesis to fuel the Krebs cycle. The levels of amino acids, nucleotides and phosphocholine in the resistant line showed significant differences from the non-resistant line, and positive correlations with the proliferation rate of CC. This study provided insights into the chemoresistance of CC from the metabolism aspect.

Gut microbiota is important for human health. The complex relationship between intestinal flora and bile acid profile has been studied previously. However, few previous studies have determined the profile and functions of bile acids in different intestinal segments, and whether they are related to the distribution of intestinal flora. In this paper, we measured the distribution of bile acids in different intestinal segments of male and female C57BL/6 mice with ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS) based targeted metabonomics analysis and nuclear magnetic resonance (NMR) based untargeted metabonomics analysis. Gender difference in distributions of bile acids were observed, which was more evident in the lower parts of intestine than in the upper part of intestine, especially in the cecum segment. This might be related to the abundance of gut microflora in different intestine segments. This study provided metabolic phenotypes of bile acids in mice of different genders, and demonstrated their interactions with gut microbiota.

The combination of doxorubicin and paclitaxel is widely used in clinical cancer therapy. Due to enhanced permeation and retention effects of nanomaterials in tumor tissues, nanocarriers with good biocompatibility have been designed to encapsulate doxorubicin/paclitaxel, and used to facilitate delivery of the drugs to achieve better therapeutic outcome. In this study, NMR-based metabonomic analyses were used to study the metabolic profiles in spleen tissues of normal healthy mice and of 4T1 tumor-bearing mice, which were treated with either saline, or doxorubicin/paclitaxel in their free forms, or doxorubicin/paclitaxel encapsulated in nanocarriers. The results demonstrated that treatment with the free forms of doxorubicin/paclitaxel remitted tumor-induced disturbances in gut microbiota, while treatment with nanocarrier-encapsulated doxorubicin/paclitaxel alleviated increased glucose and fumarate metabolism associated with tumor bearing. In contrast, tumor-related splenomegaly and metabolic alterations in amino acids, organic acids, nucleic acids and choline, both attributable to immune responses of the spleen, were not ameliorated by drug treatment. This could also be due to the fact that the treatment period was too short to have any significant effects. This work provided metabolic phenotypical information of the spleen tissues in 4T1 tumor-bearing mice, and helped to understand the metabolic impacts of drug delivery systems on the spleen.