Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway

作者：Jiabin Zhou, Yuhan Liu, Jun Chen, Nanxiang Xiong, Dongye Yi · 发表于：Drug Development Research · 年份：2023 · DOI：10.1002/ddr.22048 · 被引用次数：21 · 研究领域：Cancer Mechanisms and Therapy、Cytokine Signaling Pathways and Interactions、Quinazolinone synthesis and applications

Kaempferol (Kae) is a natural flavonoid that has multiple biological activities, such as anti-inflammatory and antitumor activities. However, few studies have been reported on antiglioma effects of Kae. This study aimed to explore the effects and potential mechanisms of Kae and synergistic antitumor activities with gefitinib (Gef) on glioma. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to detect cytotoxicity and cell proliferation. Cell apoptosis and the cell cycle were detected by flow cytometry. Transwell assays were used to detect the migratory and invasive abilities of glioma cells. Network pharmacology and molecular docking analysis were used to screen for core targets of Kae in glioma therapy. Xenograft tumor nude mice were established with U251 cells to verify the antiglioma effects of Kae in vivo. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect apoptosis in tumor tissues. The expression of proteins was detected by immunohistochemistry and western blot analysis. Kae inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G2/M phase of glioma cells in a concentration-dependent manner. Kae inhibited the migration and invasion of glioma cells at low concentrations. Network pharmacology analyses showed that epidermal growth factor receptor (EGFR) and SRC proto-oncogene (SRC) might be direct molecular-binding targets of Kae. Our results showed that Kae inhibited the levels of phosph...