1. Academic Validation
  2. Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway

Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway

  • Eur J Histochem. 2023 Aug 7;67(3). doi: 10.4081/ejh.2023.3719.
Zhongzhu Tang 1 Lei Wang 2 Yunwang Chen 3 Xiaomin Zheng 4 Runyu Wang 5 Bingxue Liu 6 Shiqi Zhang 7 Huimin Wang 8
Affiliations

Affiliations

  • 1 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. zztang2012@126.com.
  • 2 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. yxbwanglei@163.com.
  • 3 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. 2096314187@qq.com.
  • 4 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. zxm66778801@163.com.
  • 5 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. 13199349521@163.com.
  • 6 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. liubingxue0223@qq.com.
  • 7 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. www1315464550@163.com.
  • 8 Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang. wanghuimin927@sina.com.
Abstract

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.

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