Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang.
Eur J Histochem. 2023 Aug 7;67(3):3719. doi: 10.4081/ejh.2023.3719.
Quercetin (Que) has been proven to enhance the chemosensitivity of multiple cancers, including colon cancer (CC). However, whether the combination of Que and 5-fluorouracil (5-FU) has a synergistic effect on drug-resistant CC cells has not previously been reported. The effect of Que (5 and 10 μg/mL) on cell vitality and apoptosis of CC and CC drug-resistant cells was examined using a cell counting kit-8 (CCK-8) and flow cytometry. After cells were treated with 5-FU (10, 40 μg/mL), Que (10 μM, 40 μM), or 5-FU in combination with Que, cell proliferation, apoptosis, oxidative stress-related factors, reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway-related factors were examined by colony formation assay, flow cytometry, ELISA, ROS kit, immunofluorescence assay, and Western blot. The results showed that 5-FU reduced cell viability and induced apoptosis of CC as well as 5-FU-resistant CC cells. Que further restrained the proliferation, oxidative stress-related factors (SOD, CAT, GPx, and GR), ROS production, and induced apoptosis in CC cells and 5-FU-resistant CC cells induced by 5-FU. Moreover, the combination of Que and 5-FU attenuated the Nrf2/HO-1 pathway-related marker levels in CC cells and 5-FU-resistant CC cells. Therefore, our results suggest that Que reverses 5-FU resistance in CC cells via modulating the Nrf2/HO-1 pathway.
槲皮素（Que）已被证明可增强多种癌症的化学敏感性，包括结肠癌（CC）。然而，Que 与 5-氟尿嘧啶（5-FU）联合使用是否对耐药性 CC 细胞具有协同作用尚未有报道。本研究采用细胞计数试剂盒-8（CCK-8）和流式细胞术检测 Que（5 和 10 μg/mL）对 CC 和 CC 耐药细胞活力和细胞凋亡的影响。用 5-FU（10、40 μg/mL）、Que（10 μM、40 μM）或 5-FU 联合 Que 处理细胞后，通过集落形成实验、流式细胞术、ELISA、ROS 试剂盒、免疫荧光分析和 Western blot 检测细胞增殖、细胞凋亡、氧化应激相关因子、活性氧（ROS）和核因子红细胞 2 相关因子（Nrf2）/血红素加氧酶-1（HO-1）途径相关因子。结果表明，5-FU 降低了 CC 以及 5-FU 耐药 CC 细胞的活力并诱导其凋亡。Que 进一步抑制了 5-FU 诱导的 CC 细胞和 5-FU 耐药 CC 细胞的增殖、氧化应激相关因子（SOD、CAT、GPx 和 GR）、ROS 产生和诱导凋亡。此外，Que 和 5-FU 的联合使用降低了 CC 细胞和 5-FU 耐药 CC 细胞中 Nrf2/HO-1 途径相关标志物的水平。因此，我们的研究结果表明，Que 通过调节 Nrf2/HO-1 途径逆转了 CC 细胞中的 5-FU 耐药性。
