Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Urology, Tianjin 4th Center Hospital, The 4th Center Clinical College of Tianjin Medical University, Tianjin, China.
Chemosphere. 2023 Oct;339:139716. doi: 10.1016/j.chemosphere.2023.139716. Epub 2023 Aug 8.
Antimony (Sb) is a typical environmental pollutant. With the development of industrialization, antimony is widely used in daily life and enters the human body through the food chain, water source, air pollution, and other channels. The risk of antimony exposure has emerged as one of the public's major health concerns. Current research on antimony shows that antimony has certain biological toxicity, and antimony exposure may be one of the carcinogenic risk factors for bladder cancer, prostate cancer (PCa), and other cancers. But the molecular mechanism of antimony exposure in PCa is still unclear. Our results showed that serum antimony levels were significantly higher in PCa patients than in benign prostatic hyperplasia (BPH), and high levels of serum antimony were associated with poorer prognosis in PCa. We demonstrate that antimony exposure promotes PCa progression in vivo and in vitro. In addition, our results also showed that low-dose antimony exposure resulted in increased GSH, increased GPX4 expression, and decreased Fe. Since GPX4 and Fe are important molecular features in the mechanism of ferroptosis, we further found that low-dose antimony exposure can inhibit RSL3-induced ferroptosis and promote PCa proliferation. Finally, our study demonstrates that low-dose antimony exposure promotes Nrf2 expression, increases the expression level of SLC7A11, and then increases the expression of GPX4, inhibits ferroptosis, and promotes PCa progression. Taken together, our experimental results suggest that low-dose antimony exposure promotes PCa cell proliferation by inhibiting ferroptosis through activation of the Nrf2-SLC7A11-GPX4 pathway. These findings highlight the link between low-dose antimony exposure and the Nrf2-SLC7A11-GPX4 ferroptosis pathway, providing a new potential direction for the prevention and treatment of PCa.
锑（Sb）是一种典型的环境污染物。随着工业化的发展，锑被广泛应用于日常生活中，并通过食物链、水源、空气污染等途径进入人体。锑暴露的风险已成为公众主要健康关注点之一。目前的研究表明，锑具有一定的生物毒性，锑暴露可能是膀胱癌、前列腺癌（PCa）等癌症的致癌风险因素之一。但锑暴露导致 PCa 的分子机制尚不清楚。我们的研究结果表明，PCa 患者血清锑水平明显高于良性前列腺增生（BPH）患者，且高水平的血清锑与 PCa 预后不良相关。我们证明了锑暴露在体内和体外均可促进 PCa 的进展。此外，我们的研究结果还表明，低剂量的锑暴露会导致 GSH 增加、GPX4 表达增加和 Fe 减少。由于 GPX4 和 Fe 是铁死亡机制中的重要分子特征，我们进一步发现低剂量的锑暴露可抑制 RSL3 诱导的铁死亡并促进 PCa 增殖。最后，我们的研究表明，低剂量的锑暴露可促进 Nrf2 的表达，增加 SLC7A11 的表达水平，进而增加 GPX4 的表达，抑制铁死亡，促进 PCa 的进展。综上所述，我们的实验结果表明，低剂量的锑暴露通过激活 Nrf2-SLC7A11-GPX4 通路抑制铁死亡来促进 PCa 细胞增殖。这些发现强调了低剂量锑暴露与 Nrf2-SLC7A11-GPX4 铁死亡通路之间的联系，为 PCa 的防治提供了新的潜在方向。
