Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, No. 804 Shengli South Street, Xingqing District, Yinchuan City, 750004, China.
Funct Integr Genomics. 2024 Jul 16;24(4):126. doi: 10.1007/s10142-024-01402-2.
Colorectal cancer (CRC) is a prevalent malignancy affecting the human digestive tract. Triptonide has been shown to have some anticancer activity, but its effect in CRC is vague. Herein, we examined the effect of triptonide on CRC. In this study, the results of bioinformatics analysis displayed that triptonide may regulate ferroptosis in CRC by modulating GPX4 and SLC7A11. In HCT116 and LoVo cells, the expression levels of GPX4 and SLC7A11 were significantly reduced after triptonide management versus the control group. Triptonide inhibited proliferation, but promoted ferroptosis in CRC cells. SLC7A11 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide inhibited activation of the PI3K/AKT/Nrf2 signaling in CRC cells. Activation of the PI3K/AKT signaling or Nrf2 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide suppressed CRC cell growth in vivo by modulating SLC7A11 and GPX4. In conclusion, Triptonide repressed proliferation and facilitated ferroptosis of CRC cells by repressing the SLC7A11/GPX4 axis through inactivation of the PI3K/AKT/Nrf2 signaling.
结直肠癌（CRC）是一种常见的影响人类消化道的恶性肿瘤。雷公藤红素已被证明具有一定的抗癌活性，但在 CRC 中的作用尚不清楚。在此，我们研究了雷公藤红素对 CRC 的影响。在这项研究中，生物信息学分析的结果显示，雷公藤红素可能通过调节 GPX4 和 SLC7A11 来调节 CRC 中的铁死亡。在 HCT116 和 LoVo 细胞中，与对照组相比，雷公藤红素处理后 GPX4 和 SLC7A11 的表达水平明显降低。雷公藤红素抑制 CRC 细胞的增殖，但促进铁死亡。SLC7A11 的上调逆转了雷公藤红素对 CRC 细胞增殖和铁死亡的影响。雷公藤红素抑制 CRC 细胞中 PI3K/AKT/Nrf2 信号的激活。激活 PI3K/AKT 信号或上调 Nrf2 逆转了雷公藤红素对 CRC 细胞增殖和铁死亡的影响。雷公藤红素通过调节 SLC7A11 和 GPX4 抑制体内 CRC 细胞的生长。总之，雷公藤红素通过抑制 PI3K/AKT/Nrf2 信号通路抑制 SLC7A11/GPX4 轴，从而抑制 CRC 细胞的增殖并促进铁死亡。
