Abstract

Purpose

Uveal melanoma is the most common primary intraocular tumour in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. (−)-4-O-(4-O-β-D-glucopyranosylcaffeoyl) quinic acid (QA) is a new compound isolated from the endophytic fungus Penicillium sp.FJ-1 of Avicennia marina, with potent activities to inhibit the PI3K. Our work further investigated effects of QA against uveal melanoma and explored its underlying mechanisms.

Methods

MP65 cells were treated with QA at different concentrations. CCK-8 assay was used to detect effects of QA on cell viability. PI staining was used to detect cell cycle arrest. Tumour model was established by injecting MP65 cells into nude mice subcutaneously. Tumour-bearing mice were divided into three groups (5 mice per group). Mice were treated with QA (5 or 10 mg/kg) or saline by intraperitoneal injection five times per week. RT-qPCR and western blot were used to detect the expression of genes and proteins, respectively.

Results

QA significantly inhibited the proliferation of uveal melanoma cells and induced the cell cycle arrest as well as autophagy. Moreover, QA treatment significantly slowed tumour growth of uveal melanoma, shown by decreased tumour volume and weight. Furthermore, QA treatment markedly decreased the protein expression of p-PI3K and p-AKT in tumour tissues.

Conclusions

Our data provided scientific rationale to develop QA as a promising anti-tumour agent against uveal melanoma.

中文翻译：

---

(−)-4-O-(4-O-β-D-吡喃葡萄糖基咖啡酰)奎尼酸通过 PI3K/AKT 通路对葡萄膜黑色素瘤发挥抗肿瘤作用

 抽象的

 目的

葡萄膜黑色素瘤是成人最常见的原发性眼内肿瘤。没有标准的辅助治疗来预防转移，并且在转移情况下也没有有效的治疗方法。 (−)-4-O-(4-O-β-D-吡喃葡萄糖基咖啡酰)奎尼酸 (QA) 是从白骨壤内生真菌Penicillium sp.FJ-1 中分离出来的新化合物，具有有效抑制 PI3K 的活性。我们的工作进一步研究了 QA 对葡萄膜黑色素瘤的影响，并探讨了其潜在机制。

 方法

MP65 细胞用不同浓度的 QA 处理。 CCK-8测定用于检测QA对细胞活力的影响。 PI染色用于检测细胞周期停滞。采用裸鼠皮下注射MP65细胞建立肿瘤模型。将荷瘤小鼠分为三组（每组 5 只小鼠）。小鼠腹腔注射 QA（5 或 10 mg/kg）或生理盐水，每周 5 次。 RT-qPCR和western blot分别检测基因和蛋白的表达。

 结果

QA 显着抑制葡萄膜黑色素瘤细胞的增殖并诱导细胞周期停滞和自噬。此外，QA 治疗显着减缓了葡萄膜黑色素瘤的肿瘤生长，表现为肿瘤体积和重量的减小。此外，QA治疗显着降低了肿瘤组织中p-PI3K和p-AKT的蛋白表达。

 结论

我们的数据为开发 QA 作为一种有前景的葡萄膜黑色素瘤抗肿瘤药物提供了科学依据。