BACKGROUND Natural active components have been reported to serve as adjuvant medications in the clinical practice of cancer therapeutics. However, the antineoplastic roles of atractylenolide III (ATL) are rarely reported. In the present study, we assessed the functions of ATL combined with docetaxel in gastric cancer cells. METHODS Cell viability and cytotoxic activity were evaluated using CCK-8 and LDH-based cytotoxicity assays, respectively. Protein expression levels were measured by western blotting analysis. Annexin V-FITC/PI staining was used to evaluate cell apoptosis using flow cytometry. RESULTS AGS and SGC-7901 cell viability was significantly inhibited in ATL combined with docetaxel group compared with docetaxel treatment alone. The levels of LDH, apoptosis rate, and the ratio of BAX to Bcl-2 were significantly elevated in combination treatment group compared to docetaxel treatment alone. Intriguingly, docetaxel combined with ATL resulted in a significant decrease in FGFR1, FGFR2, and FGFR4 protein expression compared with docetaxel treatment alone. Knockout of FGFR1, -2, and -4 exhibited a similar role of medications to inhibit growth and induce apoptosis in AGS and SGC-7901 cells. CONCLUSIONS ATL and docetaxel treatment performed the synergistic effects on the inhibition of growth and induction of apoptosis in gastric cancer cells, and the underlying mechanism was mediated, at least partially, through the inhibition of FGFR1, -2, and -4.

中文翻译：

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白术内酯III通过抑制成纤维细胞生长因子受体1，-2和-4的表达增强多西他赛在胃癌细胞中的抗肿瘤功效。

背景技术已经报道了天然活性成分在癌症治疗的临床实践中用作辅助药物。但是，极少报道白术内酯III（ATL）的抗肿瘤作用。在本研究中，我们评估了ATL联合多西他赛在胃癌细胞中的功能。方法分别使用CCK-8和基于LDH的细胞毒性测定法评估细胞活力和细胞毒性活性。通过蛋白质印迹分析测量蛋白质表达水平。Annexin V-FITC / PI染色用于通过流式细胞仪评估细胞凋亡。结果与单独的多西他赛治疗相比，联合多西他赛组的ATL显着抑制了AGS和SGC-7901细胞的活力。LDH水平，细胞凋亡率，与单独的多西他赛治疗相比，联合治疗组中BAX与Bcl-2的比例显着升高。有趣的是，与单独的多西他赛治疗相比，多西他赛与ATL联合使用可导致FGFR1，FGFR2和FGFR4蛋白表达显着降低。FGFR1，-2和-4的敲除表现出相似的药物作用，可抑制AGS和SGC-7901细胞的生长并诱导其凋亡。结论ATL和多西他赛治疗对胃癌细胞的生长具有抑制和诱导凋亡的协同作用，其潜在机制至少部分是通过抑制FGFR1，-2和-4介导的。与单独多西他赛治疗相比，FGFR4和FGFR4的蛋白表达水平更高。FGFR1，-2和-4的敲除表现出相似的药物作用，可抑制AGS和SGC-7901细胞的生长并诱导其凋亡。结论ATL和多西他赛治疗对胃癌细胞的生长具有抑制和诱导凋亡的协同作用，其潜在机制至少部分是通过抑制FGFR1，-2和-4介导的。与单独使用多西他赛治疗相比，FGFR4和FGFR4的蛋白表达水平更高。FGFR1，-2和-4的敲除表现出相似的药物作用，可抑制AGS和SGC-7901细胞的生长并诱导其凋亡。结论ATL和多西他赛治疗对胃癌细胞的生长具有抑制和诱导凋亡的协同作用，其潜在机制至少部分是通过抑制FGFR1，-2和-4介导的。