Antitumor effect of luteolin proven by patient‐derived organoids of gastric cancer

Abstract

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.

A study related to the treatment of gastric cancer with Xiang-Sha-Liu-Jun-Zi-Tang based on network analysis

“…Its efficacy, low toxicity, and good safety make it a prospective drug for the treatment of malignant tumors [ 25 ]. Besides, In vitro and in vivo studies have shown that luteolin can inhibit GC through a variety of mechanisms, such as regulating Notch, MAPK, PI3K and other signal pathways, inducing G2/M cell cycle arrest and apoptosis [ 26 , 27 ]. Kaempferol, as another active ingredient of XSLJZT, has anti-inflammatory and anti-cancer biological activities.…”