Department of Internal Medicine, Henan University of Traditional Chinese Medicine, 450046 Zhengzhou, Henan, China.
Department of Laboratory, The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, 450000 Zhengzhou, Henan, China.
Arch Esp Urol. 2024 Mar;77(2):119-128. doi: 10.56434/j.arch.esp.urol.20247702.16.
Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary system and ferroptosis is considered as a promising therapeutic approach for treating RCC. Ginsenoside Rh4 (Rh4) was proved to have anticancer properties and play roles in ferroptosis. This study aimed to investigate the potential of ginsenoside Rh4 (Rh4) in enhancing the sensitivity of renal cell carcinoma (RCC) cells to ferroptosis and to elucidate the underlying mechanisms.
RCC cell lines of 786-O and ACHN were treated with RAS-selective lethal 3 (RSL3) and/or Rh4. Cell-viability assays were used to determine how Rh4 affected the sensitivity of RCC cells to RSL3-induced ferroptosis. Quantitative real-time polymerase chain reaction was conducted to examine the levels of ferroptosis-related genes. Additionally, the knockdown of nuclear factor E2-related factor 2 (NRF2) was performed to investigate the role of NRF2 in mediating the effects of Rh4.
RSL3 suppressed the progression of RCC cells by inducing ferroptosis. Furthermore, Rh4 led to more RCC sensitivity to ferroptosis induced by RSL3. Rh4 downregulated the ferroptosis-related gene expression including superoxide dismutase 1 ( < 0.01), glutathione peroxidase 4 ( < 0.01), and catalase ( < 0.01), which was attenuated by NRF2 knockdown. This finding suggested that Rh4 exerted its sensitising effect on ferroptosis through the NRF2 pathway.
Rh4 made RCC cells more sensitive to ferroptosis by inhibiting the NRF2 signaling and suppressing the expression of antioxidant enzymes. Therefore, combining Rh4 with ferroptosis-inducing reagents to treat RCC had potential therapeutic application.
肾细胞癌（RCC）是泌尿系统最常见的恶性肿瘤之一，铁死亡被认为是治疗 RCC 的一种很有前途的治疗方法。人参皂苷 Rh4（Rh4）已被证明具有抗癌特性，并在铁死亡中发挥作用。本研究旨在探讨人参皂苷 Rh4（Rh4）增强肾细胞癌（RCC）细胞对铁死亡敏感性的潜力，并阐明其潜在机制。
用 RAS 选择性致死 3（RSL3）和/或 Rh4 处理 RCC 细胞系 786-O 和 ACHN。细胞活力测定用于确定 Rh4 如何影响 RCC 细胞对 RSL3 诱导的铁死亡的敏感性。实时定量聚合酶链反应用于检测铁死亡相关基因的水平。此外，还进行了核因子 E2 相关因子 2（NRF2）的敲低，以研究 NRF2 在介导 Rh4 作用中的作用。
RSL3 通过诱导铁死亡抑制 RCC 细胞的进展。此外，Rh4 导致 RCC 对 RSL3 诱导的铁死亡更敏感。Rh4 下调铁死亡相关基因的表达，包括超氧化物歧化酶 1（<0.01）、谷胱甘肽过氧化物酶 4（<0.01）和过氧化氢酶（<0.01），NRF2 敲低可减弱这种作用。这一发现表明，Rh4 通过 NRF2 通路发挥其对铁死亡的敏化作用。
Rh4 通过抑制 NRF2 信号通路和抑制抗氧化酶的表达，使 RCC 细胞对铁死亡更敏感。因此，将 Rh4 与诱导铁死亡的试剂联合用于治疗 RCC 具有潜在的治疗应用。
