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<p>Prostate cancer (PCa) is one of the most prevalent malignant tumors among men globally, with limited treatment options, especially in cases that progress to castration-resistant prostate cancer (CRPC). Identifying novel molecular targets and effective therapeutic strategies is crucial for improving patient outcomes. In this study, we identified serum and glucocorticoid-regulated kinase 1 (SGK1) as a potential target of the trifluoromethylquinoline derivative TKL007. A series of in vitro assays, including CCK-8, colony formation, Transwell migration and invasion assays, and flow cytometry, were performed to systematically evaluate the anti-tumor effects of TKL007 on the PC3 and LNCaP prostate cancer cell lines. Western blot analysis revealed that TKL007 significantly inhibited the activation of the PI3K/AKT signaling pathway. Further transfection experiments confirmed that SGK1 expression levels regulate the activity of the PI3K/AKT pathway, suggesting that SGK1 may modulate this signaling axis. In vivo xenograft experiments in nude mice demonstrated that TKL007 effectively inhibited tumor growth without causing significant toxicity. Taken together, these results suggest that TKL007 exerts anti-prostate cancer effects by downregulating SGK1 protein levels and inhibiting the PI3K/AKT pathway, providing a new candidate molecule and theoretical foundation for targeted therapy.</p>

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A trifluoromethyl quinoline derivative targets SGK1 and modulates the PI3K/AKT pathway to inhibit prostate cancer progression

  • 期刊论文

  • 发表日期：

    2026年2月7日

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  • Xianhui Yang,
  • Rui Wang,
  • Guangcan Xu,
  • Ziqi Yang,
  • Xingsheng Yao,
  • Guangyang Liu,
  • Jia Yu,
  • Bixue Xu,
  • Heng Luo,
  • Ying Cao

摘要

Prostate cancer (PCa) is one of the most prevalent malignant tumors among men globally, with limited treatment options, especially in cases that progress to castration-resistant prostate cancer (CRPC). Identifying novel molecular targets and effective therapeutic strategies is crucial for improving patient outcomes. In this study, we identified serum and glucocorticoid-regulated kinase 1 (SGK1) as a potential target of the trifluoromethylquinoline derivative TKL007. A series of in vitro assays, including CCK-8, colony formation, Transwell migration and invasion assays, and flow cytometry, were performed to systematically evaluate the anti-tumor effects of TKL007 on the PC3 and LNCaP prostate cancer cell lines. Western blot analysis revealed that TKL007 significantly inhibited the activation of the PI3K/AKT signaling pathway. Further transfection experiments confirmed that SGK1 expression levels regulate the activity of the PI3K/AKT pathway, suggesting that SGK1 may modulate this signaling axis. In vivo xenograft experiments in nude mice demonstrated that TKL007 effectively inhibited tumor growth without causing significant toxicity. Taken together, these results suggest that TKL007 exerts anti-prostate cancer effects by downregulating SGK1 protein levels and inhibiting the PI3K/AKT pathway, providing a new candidate molecule and theoretical foundation for targeted therapy.