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25.06.2024 | Research

Study on the effects of rapamycin and the mTORC1/2 dual inhibitor OSI-027 on the metabolism of colon cancer cells based on UPLC-MS/MS metabolomics

verfasst von: Kai Fan, Yueyuan Wang, Jiangyujing Bian, Yewen Sun, Jiaqi Dou, Jie Pan, Yunli Yu

Erschienen in: Investigational New Drugs | Ausgabe 4/2024

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Abstract

mTORC1/2 dual inhibitors may be more effective than mTORC1 inhibitor rapamycin. However, their metabolic impacts on colon cancer cells remain unexplored. We conducted a comparative analysis of the anti-proliferative effects of rapamycin and the novel OSI-027 in colon cancer cells HCT-116, evaluating their metabolic influences through ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Our results demonstrate that OSI-027 more effectively inhibits colon cancer cell proliferation than rapamycin. Additionally, we identified nearly 600 metabolites from the spectra, revealing significant differences in metabolic patterns between cells treated with OSI-027 and rapamycin. Through VIP value screening, we pinpointed crucial metabolites contributing to these distinctions. For inhibiting glycolysis and reducing glucose consumption, OSI-027 was likely to be more potent than rapamycin. For amino acids metabolism, although OSI-027 has a broad effect as rapamycin, their effects in degrees were not exactly the same. These findings address the knowledge gap regarding mTORC1/2 dual inhibitors and lay a foundation for their further development and research.

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Titel: Study on the effects of rapamycin and the mTORC1/2 dual inhibitor OSI-027 on the metabolism of colon cancer cells based on UPLC-MS/MS metabolomics
verfasst von: Kai Fan
Yueyuan Wang
Jiangyujing Bian
Yewen Sun
Jiaqi Dou
Jie Pan
Yunli Yu
Publikationsdatum: 25.06.2024
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 4/2024
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-024-01438-y

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Study on the effects of rapamycin and the mTORC1/2 dual inhibitor OSI-027 on the metabolism of colon cancer cells based on UPLC-MS/MS metabolomics

Abstract

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