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

Sep 24, 2026

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Quercetin is reported to enhance chemosensitivity in multiple cancers, yet its potential synergy with 5-fluorouracil (5-FU) against drug-resistant colon cancer cells has remained unclear. This study evaluates how quercetin (5 and 10 μg/mL) affects cell viability and apoptosis in colon cancer (CC) and 5-FU-resistant CC cells using CCK-8 and flow cytometry. Following treatment with 5-FU, quercetin, or their combination, proliferation, oxidative stress markers, ROS, and Nrf2/HO-1 pathway factors are assessed by colony formation, ELISA, ROS assays, immunofluorescence, and Western blot. Results show quercetin suppresses proliferation and oxidative stress while promoting apoptosis, and the combination reduces Nrf2/HO-1 pathway marker levels, suggesting reversal of 5-FU resistance via Nrf2/HO-1 modulation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Quercetin as an anticancer flavonoid

Rationale for combining quercetin with 5-FU

Materials and Methods

Cell model and treatment groups

European Journal of Histochemistry 2023; volume 67:3719 Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway Zhongzhu Tang, Lei Wang, Yunwang Chen, Xiaomin Zheng, Runyu Wang, Bingxue Liu, Shiqi Zhang, Huimin Wang Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, Hangzhou, Zhejiang, China AB S TRA C T 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 drugresistant 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. Key words: colon cancer; quercetin; 5-fluorouracil; chemosensitivity; nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway. Correspondence: Huimin Wang, Department of Radiotherapy, Tongde Hospital Zhejiang Provincial, No.234, Gucui Road, Xihu District, 310014 Hangzhou, Zhejiang, [China. Email: wanghuimin927@sina.com](China. Email: wanghuimin927@sina.com) Contributions: ZT, HW, conception and design of the research, manuscript drafting and revision for important intellectual content; LW, YC, XZ, RW, BL, SZ,data acquisition, analysis and interpretation, statistical analysis All the authors read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work. Conflict of interest: the authors declare no conflict of interest. Availability of data and material: the analyzed data sets generated during the present study are available from the corresponding author upon reasonable request. [European Journal of Histochemistry 2023; 67:3719] Article Introduction Colon cancer (CC) is the third most common malignancy in men and the second most common cancer in the world.1 At present, the pathogenic factors of CC include a high-fat diet, insufficient fiber intake, unhealthy lifestyle, and the interaction between genetic and environmental factors.2 The early symptoms of CC patients are not obvious; approximately 40% of patients can be diagnosed and treated at the early stage of the disease, and the survival rate of advanced patients is as low as 12.5%.3,4 According to the Guidelines for the Diagnosis and Treatment of Colorectal Cancer by the Chinese Society of Clinical Oncology and Clinical Practice Guidelines of American Society of Cataract and Refractive Surgery, for adjuvant therapy, 5-fluorouracil (5-FU) is the major chemotherapeutic drug recommended for use. 5-FU can block the DNA synthesis and proliferation of cancer cells by interfering with their nucleic acid metabolism.5 However, chemotherapeutic drugs are considered a “double-edged sword”. Adverse reactions also occur when cancer cells are inhibited. The insensitivity ofCC cells to 5-FU is the main reason for the decreased survival rate in CC patient

FAQs

What problem does the study address regarding colon cancer therapy?

The study targets drug resistance of colon cancer cells to 5-FU, which reduces patient survival, and evaluates whether quercetin can reverse this resistance.

How were quercetin and 5-FU effects on the cells measured?

Cell vitality and apoptosis were assessed with a CCK-8 assay and flow cytometry, while proliferation, oxidative stress factors, ROS, and Nrf2/HO-1 pathway-related markers were examined using colony formation, ELISA, ROS kits, immunofluorescence, and Western blot.

What mechanism is proposed for how quercetin reverses 5-FU resistance?

The results indicate that quercetin, alone and combined with 5-FU, attenuates Nrf2/HO-1 pathway-related marker levels, suggesting resistance reversal via Nrf2/HO-1 pathway modulation.

Sep 24, 2026

Uploaded by Rizky