Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway - 09/10/21
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Abstract |
Aim |
To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism.
Materials and methods |
Targets of the drug promethazine (PMTZ) were identified by DrugBank and comparative toxicogenomic databases (CTD), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed with STRING software. The effects of PMTZ were predicted to be associated with the PI3K/AKT pathway. Cell Counting Kit 8 (CCK-8) assays were used to evaluate the effects of different concentrations of PMTZ on the proliferation of various types of CRC cells. Flow cytometry and Western blotting analyses were used to detect the degree of CRC cell apoptosis and the expression of the apoptosis-related proteins Bcl-2, Bax and caspase-3 after PMTZ treatment. The expression levels of PI3K/AKT pathway-related proteins [PI3K, AKT, phosphorylated (P)-PI3K and p-AKT] in CRC cells treated with PMTZ were analyzed by Western blotting.
Results |
PMTZ inhibited the proliferation and promoted the apoptosis of CRC cells and suppressed the activation of the PI3K/AKT signaling pathway in a dose-dependent manner.
Discussion and conclusions |
PMTZ may suppress the proliferation and induce the apoptosis of CRC cells by inhibiting the PI3K/ AKT signaling pathway. This study reported, for the first time, the function of PMTZ in CRC cells and the underlying mechanism and further confirmed the potential antitumor effects of phenothiazine. The combination of bioinformatics analyses and experiments provides informative evidence for the reuse of drugs and the development of new drugs.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells. |
• | Promethazine may induce mitochondrial apoptosis through PI3K/AKT pathway to suppress colorectal cancer cells. |
• | The combination of bioinformatics and basic experiments provides new evidence for the discovery of innovative therapeutic drugs related to colorectal cancer. |
• | The role of promethazine in colorectal cells and the underlying molecular mechanism was elucidated for the first time. |
Keywords : colorectal cancer, promethazine, apoptosis, PI3K/AKT pathway, drug repurposing
Plan
Vol 143
Article 112174- novembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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