Therefore, it is urgent to identify novel therapeutic strategies or targets for CRC treatment. Despite dramatic improvements leading to longer overall patient survival in recent decades, the 5-year survival ratio (approximately 57%) for CRC is still unsatisfactory in China (Zhu et al., 2017). In a clinical setting, the therapeutic regimens for CRC patients include surgical resection, targeted therapy, chemotherapy, radiotherapy, and immunotherapy (Brenner, Kloor, & Pox, 2014 Doitsh et al., 2017). According to an estimation, there were approximately 1,800,977 new cases of CRC and 861,663 associated deaths worldwide in 2018 (Bray et al., 2018 Ferlay et al., 2019). CRC is the third most frequently diagnosed malignancies and the second leading cause of cancer-related deaths. In colorectal cancer (CRC), malignant cells form in the tissues of the colon and rectum. Penfluridol triggers mitochondrial-mediated apoptosis and induces glycolysis inhibition via modulating HK-2 in CRC and provides a theoretical basis to support penfluridol as a repurposed drug for CRC patients. Consistent with in vitro results, penfluridol could also suppress tumor growth and trigger apoptosis in vivo. The proapoptotic effect and glycolytic inhibition-induced by penfluridol were effectively reversed by HK-2 overexpression. Further mechanistic studies revealed that penfluridol influenced cell apoptosis and glycolysis in CRC cells by downregulating hexokinase-2 (HK-2). Furthermore, the process of glycolysis in HCT-116 and HT-29 cells was inhibited upon penfluridol treatment, as evidenced by the decrease in glucose consumption, lactate production, and intracellular ATP levels. Penfluridol reduced cell survival and promoted apoptotic cell death effectively through the mitochondria-mediated intrinsic pathway in a dose-dependent manner. A CRC xenograft tumor model was used to validate the antitumor activity of penfluridol in vivo. Mitochondrial membrane potential was detected using JC-1 staining. The protein levels of related genes were detected through western blotting. Caspase-3 activity, glucose consumption, lactate production, and intracellular ATP levels were evaluated using the corresponding commercial detection kits. The cell apoptosis and cell cycle distribution were quantified through flow cytometry.
Cell viability and clonogenic potential were detected by the cell counting kit-8 and colony formation assay. Here, we investigated the effect of penfluridol on the biological behavior of colorectal cancer (CRC) cells. Go back to the app and try signing in again.Penfluridol, a commonly used antipsychotic agent in a clinical setting, exhibits potential anticancer properties against various human malignancies.Enter your username and password, then enter the letters on the screen.If you still can’t sign in to your account on the app, try the following:
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