Chen Yu-Hsi, Li Chi-Huan, Liu Shih-Wei, Hsu Fei-Ting, Ku Ming-Chou
Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Department of Orthopedics, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Anticancer Res. 2025 Apr;45(4):1465-1480. doi: 10.21873/anticanres.17530.
BACKGROUND/AIM: Osteosarcoma (OSCC) remains a significant health concern, necessitating novel therapeutic strategies. This study investigated the anti-tumor effects of fluoxetine in an OSCC model.
Mice inoculated with U-2 OS cells were treated with fluoxetine (10 or 20 mg/kg) to evaluate tumor growth, metastasis, and underlying molecular mechanisms.
Fluoxetine treatment resulted in a dose-dependent reduction in tumor volume and weight, without causing systemic toxicity, as confirmed by histopathological and biochemical analyses. Mechanistically, fluoxetine activated caspase-dependent apoptosis by up-regulating cleaved caspase-8, caspase-9, and caspase-3. It also inhibited OSCC metastasis by suppressing VEGF and MMP-9 expression, reducing epithelial-mesenchymal transition markers. Furthermore, fluoxetine significantly reduced the phosphorylation of AKT, PRAS40, mTOR, and NF-[Formula: see text]B, thereby disrupting key tumorigenic signaling pathways.
Fluoxetine demonstrates promising anti-tumor activity in OSCC by inducing apoptosis, inhibiting metastasis, and targeting oncogenic signaling pathways. These findings suggest that fluoxetine may serve as a potential therapeutic agent for OSCC, warranting further investigation for clinical application.
背景/目的：骨肉瘤（OSCC）仍然是一个重大的健康问题，需要新的治疗策略。本研究调查了氟西汀在骨肉瘤模型中的抗肿瘤作用。
用氟西汀（10或20mg/kg）处理接种U-2 OS细胞的小鼠，以评估肿瘤生长、转移及潜在的分子机制。
组织病理学和生化分析证实，氟西汀治疗导致肿瘤体积和重量呈剂量依赖性减少，且未引起全身毒性。从机制上讲，氟西汀通过上调裂解的半胱天冬酶-8、半胱天冬酶-9和半胱天冬酶-3激活半胱天冬酶依赖性凋亡。它还通过抑制VEGF和MMP-9表达、减少上皮-间质转化标志物来抑制骨肉瘤转移。此外，氟西汀显著降低AKT、PRAS40、mTOR和NF-[公式：见正文]B的磷酸化，从而破坏关键的致癌信号通路。
氟西汀通过诱导凋亡、抑制转移和靶向致癌信号通路，在骨肉瘤中显示出有前景的抗肿瘤活性。这些发现表明氟西汀可能作为骨肉瘤的一种潜在治疗药物，值得进一步研究其临床应用。
