Proapoptotic Effect of Icariin on Human Ovarian Cancer Cells via the NF-κB/PI3K-AKT Signaling Pathway: A Network Pharmacology-Directed Experimental Investigation.
| Autor: | Gao, Jingjing, Fu, Yanjin, Song, Linliang, Long, Mengsha, Zhang, Yiyao, Qin, Jiajia, Liu, Haiquan |
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| Předmět: |
PROTEIN kinases
IN vitro studies REVERSE transcriptase polymerase chain reaction STATISTICS HERBAL medicine OVARIAN tumors STAINS & staining (Microscopy) PHOSPHOTRANSFERASES ONCOGENES WESTERN immunoblotting ONE-way analysis of variance APOPTOSIS SIGNAL peptides CELLULAR signal transduction BIOINFORMATICS GENE expression T-test (Statistics) DNA-binding proteins CELL proliferation DESCRIPTIVE statistics RESEARCH funding CELL lines PHARMACEUTICAL chemistry POLYMERASE chain reaction DATA analysis software DATA analysis CHINESE medicine CASPASES PHOSPHORYLATION |
| Zdroj: | American Journal of Chinese Medicine; 2022, Vol. 50 Issue 2, p589-619, 31p |
| Abstrakt: | Based on network pharmacology tools and public bioinformatics databases, the pharmacodynamic target and key mechanism of icariin (ICA) in the treatment of ovarian cancer (OC) were identified and experimentally verified. Our previous research showed that TNF, MMP9, STAT3, PIK3CA, ERBB2, MTOR, IL2, PTGS2, KDR and F2 are important targets of ICA in the treatment of OC. TNF, as a hub gene in tumor tissues, was associated with poor prognosis. ICA acted on OC mainly through the biological functions of various kinases, and the pathway with the highest accuracy (p -value) was PI3K. Meanwhile, we observed a close upstream and downstream relationship between NF- κ B and the Pl3K-AKT pathway. This study further verified the mechanism of ICA in promoting apoptosis of SKOV3 cells through the NF- κ B signaling pathway and the tandem relationship between NF- κ B and the Pl3K-AKT pathway. The assay results demonstrated that ICA can promote the apoptosis of SKOV3 cells as indicated by the proapoptotic markers Bax, Bcl-xl and Caspase-3 and the key factors of the NF- κ B signaling pathway (NF- κ Bp65, p-NF- κ Bp65, p-I κ B α and I κ B α). ICA can block the classical NF- κ B pathway by inhibiting I κ B α phosphorylation and consequently blocking the activation of the NF- κ B pathway in SKOV3 cells. ICA can also promote apoptosis by blocking the activation of the NF- κ B pathway in SKOV3 cells via inhibition of NF- κ Bp65 nuclear translocation. After using a PI3K pathway inhibitor, we further discovered that ICA may reduce AKT signal transduction by inhibiting the level of Akt phosphorylation, resulting in a loss of PI3K/Akt-dependent activation of the NF- κ B pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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