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槲皮素增强乳腺癌患者来源类器官的化疗敏感性。

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

作者信息

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

机构信息

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.

Department of Breast and Thyroid Surgery, Bengbu First People's Hospital, Bengbu, Anhui Province, People's Republic of China.

出版信息

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

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.

摘要

目的

本研究旨在从乳腺癌(BC)患者的组织中培养类器官,并使用这些类器官来测定对槲皮素及其与化疗药物联合使用的敏感性。

方法

培养了4个源自患者的BC类器官(PDO)。在不同代次及复苏后评估PDO的增殖活性和形态。采用苏木精-伊红(H&E)染色和免疫组织化学(IHC)染色来鉴定病理变化和生物标志物的表达。使用三磷酸腺苷(ATP)活力测定法评估对槲皮素、化疗药物及其组合的敏感性。

结果

我们成功地从BC组织中获得了所有PDO。PDO在传代过程中保持了其活性和形态。此外,每个PDO的雌激素受体(ER)、人表皮生长因子受体(HER2)和Ki67的病理变化和表达模式与其原始组织一致。所有4个PDO对槲皮素高度敏感,其半数抑制浓度(IC50)值均小于22μM。PDO对多西他赛和盐酸表柔比星表现出较好的敏感性,但对顺铂的敏感性较低。与槲皮素联合使用可提高对三种化疗药物的敏感性。特别是,顺铂的IC50值大幅下降。

结论

我们成功地从BC患者中建立了PDO,并证明槲皮素可提高这些PDO对化疗药物的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b988/11668317/6af86d058840/BCTT-16-993-g0001.jpg

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