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Simvastatin Induces Metabolic Reprogramming and Increases the Antitumor Effect of 3-Bromopyruvate

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In the process of tumor development, cancer cells rely on a variety of different metabolic pathways, such as aerobic glycolysis (Warburg effect), to support tumor proliferation and adapt to poor environments according to the needs of different periods. Reprogramming of metabolism patterns in tumors cause failure of tumor therapy which is targeting a single metabolic pathway. In this study, simvastatin promotes the glycolysis flux and oxidative phosphorylation in tumor cells. Hence, simvastatin steering tumor cells in a metabolic pattern that relies on glycolysis as an energy source for proliferation. Therefore, we intended to use this characteristic to develop novel anti-tumor treatment strategies, where we introduced an effective glycolytic inhibitor 3-Bromopyruvate and employed a drug combination with simvastatin. The combination of simvastatin and 3-Bromopyruvate significantly inhibits the growth, proliferation, migration, and invasion of colorectal cancer cells, which exhibits a better anti-tumor effect than when used alone.

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