Background

Previous studies have shown similarities in the metabolism of cancer cells and parasites, suggesting that antiparasitic drugs may be used as anticancer agents. Remdesivir (Rem), an RdRp inhibitor, has been recently used in SARS-CoV-2 pandemic. Although the apoptotic effect of Rem has been demonstrated on the SKOV3 ovarian cancer cell line, its cytotoxic effect has not been analyzed in different cancer cells.

Objective

We aimed to evaluate its cell death-inducing effects on PC3 prostate cancer, HepG2 hepatocellular carcinoma, and A2058 malignant melanoma cells for the first time, using WST-1, Annexin V, cell cycle analysis, AO/EB staining, live-cell imaging, TEM, and gene expression analysis.

Results

Rem treatment at 10, 25, and 50 µM significantly decreased cell viability in all cancer cells (p < 0.01). While Rem triggered apoptosis in PC3, vacuole-dependent cell death was detected in HepG2 cells by visualizing the cells with TEM and time-dependent live-cell imaging. Moreover, both forms of cell death were triggered together in A2058. The formation of AVOs were observed more after 12 h and 24 h in HepG2 and A2058 cells, respectively. Additionally, Rem significantly induced cell cycle arrest in the G2/M (p < 0.01). Finally, the mRNA levels of autophagic markers, Atg12, Atg5, p62, Beclin, and LC3, were significantly increased in A2058 and HepG2 (p < 0.01) compared to control groups.

Conclusions

Our results suggest that Rem has promising cytotoxic effects on various cancer cells. However, it triggers different types of cell death in different cancer types, indicating that further studies should focus on clarifying the molecular mechanism of the specific action of Rem.

中文翻译：

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抗病毒RdRp抑制剂Remdesivir对不同癌细胞的体外细胞毒和抗肿瘤作用

背景

先前的研究表明癌细胞和寄生虫的代谢有相似之处，这表明抗寄生虫药物可以用作抗癌药物。瑞德西韦 (Rem) 是一种 RdRp 抑制剂，最近已用于治疗 SARS-CoV-2 大流行。尽管Rem的细胞凋亡作用已在SKOV3卵巢癌细胞系中得到证实，但其细胞毒性作用尚未在不同的癌细胞中进行分析。

客观的

我们旨在利用 WST-1、Annexin V、细胞周期分析、AO/EB 染色、活细胞成像、TEM 和基因表达分析，首次评估其对 PC3 前列腺癌、HepG2 肝细胞癌和 A2058 恶性黑色素瘤细胞的细胞死亡诱导作用。

结果

10、25 和 50 µM 的 Rem 处理显着降低了所有癌细胞的细胞活力 ( p  < 0.01)。Rem 触发 PC3 细胞凋亡，而通过使用 TEM 和时间依赖性活细胞成像观察细胞，在 HepG2 细胞中检测到液泡依赖性细胞死亡。此外，两种形式的细胞死亡在 A2058 中同时触发。在 HepG2 和 A2058 细胞中分别在 12 小时和 24 小时后观察到更多的 AVO 形成。此外，Rem 显着诱导 G2/M 期细胞周期停滞（p  < 0.01）。 最后，与对照组相比， A2058 和 HepG2 中自噬标记Atg12、Atg5、p62、Beclin 和 LC3的 mRNA 水平 显着增加 ( p < 0.01)。

结论

我们的结果表明 Rem 对多种癌细胞具有良好的细胞毒作用。然而，它在不同的癌症类型中引发不同类型的细胞死亡，表明进一步的研究应集中于阐明Rem具体作用的分子机制。