Huang Chien-Jung, Shieh Po-Chuen, Yang Jai-Sing, Li Yi-Chia, Chiu Yu-Jen, Bau DA-Tian, Hung Chih-Hsin
Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan, R.O.C.
Department of Pharmacy, Tajen University, Pingtung, Taiwan, R.O.C.
Anticancer Res. 2025 Feb;45(2):511-523. doi: 10.21873/anticanres.17440.
BACKGROUND/AIM: Gastric cancer (GC) is one of the most common cancers worldwide. Cisplatin is a key therapeutic agent for treating GC. Currently, the resistance of GC cells to cisplatin remains a major concern. Pterostilbene (PTS) is a natural phytochemical found in blueberry and grape. The anti-cisplatin-resistant GC effects and pharmacological mechanisms of PTS are unknown.
We investigated the anticancer activity of PTS in cisplatin-resistant GC cells and explored its pharmacological mechanisms of action via cell viability assay, cell confluence assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, acridine orange (AO) staining, monodansylcadaverine (MDC) staining, caspase-9/-3 activity assay, and RNA sequencing (RNA-Seq) analysis.
Our results showed that PTS inhibited cell viability and cell confluence of cisplatin-resistant GC cells using the CCK-8 assay and the IncuCyte S3 ZOOM System. The TUNEL assay showed that PTS promoted apoptosis in cisplatin-resistant GC cells. PTS induced apoptosis by increasing caspase-9 and caspase-3 activity. PTS promoted cell autophagy by increasing vacuole formation and acidic vesicular organelles using MDC and AO staining. We also observed an increase in the expression of LC3B in PTS-treated cisplatin-resistant GC cells. RNA-Seq analysis demonstrated that PTS induced apoptosis and autophagy in cisplatin-resistant GC cells by decreasing the expression of ATM/ATR, HIF-1, PI3K, RB1CC, TBK1, and mitochondria-related genes.
Our results suggested that PTS is a promising phytochemical for GC therapy, particularly against cisplatin resistance.
背景/目的：胃癌（GC）是全球最常见的癌症之一。顺铂是治疗GC的关键治疗药物。目前，GC细胞对顺铂的耐药性仍然是一个主要问题。紫檀芪（PTS）是一种存在于蓝莓和葡萄中的天然植物化学物质。PTS对顺铂耐药GC的抗癌作用及其药理机制尚不清楚。
我们通过细胞活力测定、细胞汇合度测定、末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色、吖啶橙（AO）染色、单丹磺酰尸胺（MDC）染色、caspase-9/-3活性测定和RNA测序（RNA-Seq）分析，研究了PTS在顺铂耐药GC细胞中的抗癌活性，并探讨其药理作用机制。
我们的结果表明，使用CCK-8测定法和IncuCyte S3 ZOOM系统，PTS抑制了顺铂耐药GC细胞的活力和细胞汇合度。TUNEL测定表明，PTS促进了顺铂耐药GC细胞的凋亡。PTS通过增加caspase-9和caspase-3活性诱导凋亡。PTS通过使用MDC和AO染色增加液泡形成和酸性细胞器来促进细胞自噬。我们还观察到PTS处理的顺铂耐药GC细胞中LC3B的表达增加。RNA-Seq分析表明，PTS通过降低ATM/ATR、HIF-1、PI3K、RB1CC、TBK1和线粒体相关基因的表达，诱导顺铂耐药GC细胞凋亡和自噬。
我们的结果表明，PTS是一种有前途用于GC治疗的植物化学物质，特别是针对顺铂耐药性。
