Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing, China.
Phytother Res. 2023 Nov;37(11):5315-5327. doi: 10.1002/ptr.7963. Epub 2023 Jul 19.
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.
木樨草素（Lut）已被证明可抑制胃癌（GC）；然而，其在人类样本中与其他临床药物的疗效尚未被检测。本研究旨在阐明 Lut 在 GC 患者来源类器官（PDO）中的抗肿瘤活性。PDO 是从 GC 癌组织中建立的，使用全外显子组测序对组织和 PDO 进行了表征。通过用 Lut、去甲斑蝥素（NCTD）和卡铂（CP）处理 PDO 来进行药物敏感性测试。通过对 PDO 进行 RNA 测序来阐明 Lut 的抗肿瘤机制，并在三个 GC 细胞系中进一步验证。成功构建了 11 个 PDO，它们与相应肿瘤的病理生理学和遗传变化高度一致。PDO 的 Lut、NCTD 和 CP 的 IC50 分别为 27.19、23.9 和 37.87 μM。Lut 处理上调了 GC 细胞系中 FOXO3、DUSP1 和 CDKN1A 的表达，下调了 IL1R1 和 FGFR4 的表达，与 PDO 的结果一致。我们证明，Lut 比 CP 具有更强的抗肿瘤作用，但与 NCTD 的作用相似，这是在体外 PDO 系统中获得的。此外，Lut 对 PDO 表现出不同程度的抗肿瘤作用，这表明 PDO 可能是个性化治疗的有用临床前药物筛选工具。
