铁死亡是一种铁依赖性的、区别于凋亡和自噬的新型细胞死亡方式，它参与中药抗肿瘤的机制尚不明确。课题组前期研究发现：中药单体汉黄芩苷（WGS）能抑制前列腺癌细胞的增殖和侵袭，而铁死亡抑制剂能阻断WGS的上述作用；这提示WGS可能通过诱导铁死亡，进而发挥抗肿瘤的功效。Nrf2是介导细胞氧化应激和铁死亡的重要因子，GSK-3β能抑制Nrf2的活性并加剧氧化应激损伤，但GSK-3β、Nrf2与铁死亡的关系尚未见报道。前期预实验发现WGS能调节前列腺癌细胞内GSK-3β和Nrf2的活性。我们推测：WGS通过GSK-3β/Nrf2途径诱导前列腺癌细胞铁死亡，进而抑制细胞增殖和侵袭。本研究拟采用体外细胞学实验和裸鼠体内实验，进一步验证：1、WGS诱导的铁死亡能否抑制前列腺癌细胞增殖和侵袭；2、WGS是否通过GSK-3β/Nrf2途径诱导铁死亡。本研究将为中药抗肿瘤的临床应用提供新靶点和新思路。

Ferroptosis is an iron dependent cell death mode, which is different from apoptosis and autophagy. However, the mechanism of its participation in anti-tumor of traditional Chinese medicine is not clear. Our previous study found that the Chinese herbal monomer wogonoside (WGS) can inhibit the proliferation and invasion of prostate cancer cells, while the ferroptosis inhibitor can block the above effects of WGS; this suggests that WGS may play an anti-tumor role by inducing ferroptosis. Nrf2 is an important factor that mediates cell oxidative stress and ferroptosis. GSK-3β can inhibit Nrf2 activity and aggravate oxidative stress response, but the relationship between GSK-3β, Nrf2 and ferroptosis has not been reported. Our preliminary studies showed that WGS can regulate the activities of GSK-3β and Nrf2 in prostate cancer cells. We hypothesize that WGS can induce ferroptosis of prostate cancer cells through GSK-3β/Nrf2 pathway, and then inhibit cell proliferation and invasion. This study will further verify in vivo and in vitro: 1. Whether WGS induced ferroptosis can inhibit the proliferation and invasion of prostate cancer cells; 2. Whether WGS can induce ferroptosis through GSK-3β/Nrf2 pathway. This study will provide new targets and new ideas for the anti-tumor application of traditional Chinese medicine.