Quercetin Promote the Chemosensitivity in Organoids Derived from Patients with Breast Cancer

Shengwen Meng; Yifan Cao; Lei Lu; Xuanhe Li; Siyu Sun; Fangqian Jiang; Jianfei Lu; Dongwei Fan; Xinxin Han; Tingjing Yao

doi:10.2147/BCTT.S494901

Quercetin Promote the Chemosensitivity in Organoids Derived from Patients with Breast Cancer

Breast Cancer (Dove Med Press). 2024 Dec 20:16:993-1004. doi: 10.2147/BCTT.S494901. eCollection 2024.

Authors

Shengwen Meng¹, Yifan Cao¹, Lei Lu¹, Xuanhe Li¹, Siyu Sun¹, Fangqian Jiang¹, Jianfei Lu², Dongwei Fan³, Xinxin Han¹, Tingjing Yao¹

Affiliations

¹ Department of Surgical Oncology, The Fourth Ward of Breast and Thyroid, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, People's Republic of China.
² Department of Breast and Thyroid Surgery, Bengbu First People's Hospital, Bengbu, Anhui Province, People's Republic of China.
³ Department of General Surgery, Affiliated Hospital of West Anhui Health Vocational College, Luan, Anhui Province, People's Republic of China.

Abstract

Aim: The study aimed to culture organoids from tissues of patients with breast cancer (BC) and use the organoids to measure the sensitivity to quercetin and its combination with chemotherapeutic agents.

Methods: Four patient-derived organoids (PDOs) of BC were cultured. The proliferative activity and morphology of PDOs were evaluated on different generations and after resuscitation. H&E and immunohistochemical (IHC) staining were used to identify the pathological changes and the expression of biomarkers. The sensitivity to quercetin and chemotherapeutic agents and their combinations were evaluated using adenosine triphosphate (ATP) viability assays.

Results: We successfully obtained all PDOs from BC tissues. PDOs preserved their activity and morphology during generation passage. In addition, the pathological changes and expression patterns of estrogen receptor (ER), human epidermal growth factor receptor (HER2), and Ki67 of each PDO were consistent with their original tissues. All four PDOs were highly sensitive to quercetin, and their IC50 values were less than 22 μM. PDOs showed better sensitivity to docetaxel and epirubicin hydrochloride, but less sensitivity to cis-platinum. Combination with quercetin promoted the sensitivity to three chemotherapeutic agents. In particular, the IC50 value of cis-platinum greatly decreased.

Conclusion: We successfully established PDOs from patients with BC and demonstrated that quercetin can promote the sensitivity of chemotherapeutic agents in these PDOs.

Keywords: breast cancer; drug sensitivity; patient-derived organoids; quercetin.

Grants and funding

This study was funded by the Natural Science Project of Bengbu Medical College (Byycx22049), Natural Science Research Project of Anhui Educational Committee (KJ2020A0577), and the Anhui Provincial Health Research Project (AHWJ2023A30031).