Background

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor developing from epithelial linings of nasopharynx, and 10–50 out of 100,000 NPC cases were recorded globally particularly in the Asian countries.

Methodology

The cytotoxicity of geraniin against the NPC C666-1 cells were analyzed using MTT assay. The influences of geraniin on the C666-1 cell viability with the presence of ROS and apoptosis inhibitors were also studied. The expressions of PI3K, Akt, mTOR, and autophagic markers LC3, ATG7, P62/SQSTM1 expressions in the C666-1 cells were studied by western blotting analysis. The ROS production was assayed using DCFH-DA staining. The immunofluorescence assay was performed to detect the NF-κB and β-catenin expressions in the C666-1 cells.

Results

The cell viability of C666-1 cells were appreciably prevented by the geraniin. The geraniin treatment also inhibited the C666-1 cell growth with the presence of apoptotic inhibitor Z-VAD-FMK. The geraniin-treatment effectively improved the ROS production and inhibited the NF-κB and β-catenin expressions in the C666-1 cells. Geraniin appreciably modulated the PI3K/Akt/mTOR signaling axis and improved the autophagy-mediated cell death via improving the autophagic markers LC3 and ATG7 expressions in the C666-1 cells.

Conclusion

In conclusion, our results proved that geraniin inhibits C666-1 cell growth and initiated autophagy-mediated cell death via modulating PI3K/Akt/mTOR cascade and improving LC3 and ATG7 expressions in the C666-1. Geraniin and it could be a hopeful and efficient candidate to treat the human NPC in the future.

中文翻译：

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Geraniin 在鼻咽癌 C666-1 细胞中抑制细胞生长并促进自噬介导的细胞死亡

背景

鼻咽癌 (NPC) 是一种罕见的从鼻咽上皮层发展而来的恶性肿瘤，全球 100,000 例 NPC 病例中有 10-50 例记录在案，尤其是在亚洲国家。

方法

使用MTT法分析老鹳草素对NPC C666-1细胞的细胞毒性。还研究了在存在 ROS 和凋亡抑制剂的情况下，香叶苷对 C666-1 细胞活力的影响。通过蛋白质印迹分析研究C666-1细胞中PI3K、Akt、mTOR和自噬标志物LC3、ATG7、P62/SQSTM1的表达。使用 DCFH-DA 染色测定 ROS 的产生。进行免疫荧光测定以检测C666-1细胞中NF-κB和β-连环蛋白的表达。

结果

C666-1 细胞的细胞活力明显被老鹳草素阻止。在凋亡抑制剂 Z-VAD-FMK 的存在下，香叶苷处理还抑制了 C666-1 细胞的生长。香叶苷处理有效地改善了 C666-1 细胞中 ROS 的产生并抑制了 NF-κB 和 β-catenin 的表达。Geraniin 显着调节 PI3K/Akt/mTOR 信号轴，并通过改善 C666-1 细胞中自噬标志物 LC3 和 ATG7 的表达来改善自噬介导的细胞死亡。

结论

总之，我们的结果证明，香叶苷通过调节 PI3K/Akt/mTOR 级联反应和改善 C666-1 中 LC3 和 ATG7 的表达来抑制 C666-1 细胞生长并引发自噬介导的细胞死亡。Geraniin，它可能是未来治疗人类 NPC 的有希望和有效的候选者。