Antitumor effect of luteolin proven by patient-derived organoids of gastric cancer.


Journal

Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486

Informations de publication

Date de publication:
Nov 2023
Historique:
revised: 03 07 2023
received: 06 03 2023
accepted: 04 07 2023
medline: 10 11 2023
pubmed: 20 7 2023
entrez: 20 7 2023
Statut: ppublish

Résumé

Luteolin (Lut) has been shown to inhibit gastric cancer (GC); however, its efficacy compared to other clinical drugs has not been examined in human samples. This study aimed to elucidate the antitumor activity of Lut in GC patient-derived organoids (PDOs). PDOs were established from GC cancer tissues, and the characterization of tissues and PDOs was performed using whole-exome sequencing. Drug sensitivity tests were performed by treating PDOs with Lut, norcantharidin (NCTD), and carboplatin (CP). RNA sequencing of PDOs was performed to elucidate the antitumor mechanism of Lut, which was further verified in three GC cell lines. Eleven PDOs were successfully constructed, and were highly consistent with the pathophysiology and genetic changes in the corresponding tumors. The IC50s of Lut, NCTD, and CP of PDOs were 27.19, 23.9, and 37.87 μM, respectively. Lut treatment upregulated FOXO3, DUSP1, and CDKN1A expression and downregulated IL1R1 and FGFR4 expression in GC cell lines, which was consistent with the results of PDOs. We demonstrate that Lut exerted stronger antitumor effects than CP, but a similar effect to that of NCTD, which was obtained in an in vitro PDO system. Additionally, Lut exerted varying degrees of antitumor effects against the PDOs, thereby indicating that PDO may be a useful preclinical drug screening tool for personalized treatment.

Identifiants

pubmed: 37469042
doi: 10.1002/ptr.7963
doi:

Substances chimiques

Luteolin KUX1ZNC9J2
Carboplatin BG3F62OND5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5315-5327

Subventions

Organisme : National Natural Science Foundation of China
ID : 82070577

Informations de copyright

© 2023 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.

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Auteurs

Xinyu Hao (X)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

Ming Zu (M)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

Jing Ning (J)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

Xin Zhou (X)

Department of General Surgery, Peking University Third Hospital, Beijing, China.

Yueqing Gong (Y)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

Xiurui Han (X)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

Qiao Meng (Q)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

Dong Li (D)

Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing, China.

Shigang Ding (S)

Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.

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