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Effects of oxysterol Oxy186 and Oxy210 on A549 xenograft tumor growth

ABSTRACT: Effects of oxysterol Oxy186 and Oxy210 on A549 xenograft tumor growth

PROVIDER: PRJNA820180 | ENA |

REPOSITORIES: ENA

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Effects of oxysterol Oxy186 and Oxy210 on A549 xenograft tumor growth

Project description:To examine the efficacy of oxysterols in inhibiting tumor growth in vivo, we tested Oxy186 and Oxy210 in subcutaneous xenograft tumor models constructed with A549 cells in nude mice. After the tumor size reached an average of ~100 mm3, the compounds were administered daily via oral gavage at 50 mg/kg. We found that Oxy186 started to inhibit tumor growth at day 8, and significantly reduced the tumor volume from day 11 to day18 of treatment, compared to that of vehicle control. Surprisingly, Oxy210 did not show such inhibitory effect.

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Project description:The application of ketogenic diet (KD) (high fat/low carbohydrate/adequate protein) as an auxiliary cancer therapy is a field of growing attention. KD provides sufficient energy supply for healthy cells, while possibly impairing energy production in highly glycolytic tumor cells. Moreover, KD regulates insulin and tumor related growth factors (like insulin growth factor-1, IGF-1). In order to provide molecular evidence for the proposed additional inhibition of tumor growth when combining chemotherapy with KD, we applied untargeted quantitative metabolome analysis on a spontaneous breast cancer xenograft mouse model, using MDA-MB-468 cells. Healthy mice and mice bearing breast cancer xenografts and receiving cyclophosphamide chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of adjuvant KD in the context of tumor growth inhibition and suggest additional mechanisms of tumor suppression beyond the proposed constrain in energy supply of tumor cells.

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