Department of Urology, Shaanxi Provincial People's Hospital, 256 West Youyi Road, Xi'an, Shaanxi 710068, China.
Department of Urology, Shaanxi Provincial People's Hospital, 256 West Youyi Road, Xi'an, Shaanxi 710068, China.
Eur J Pharmacol. 2018 May 5;826:24-30. doi: 10.1016/j.ejphar.2018.02.038. Epub 2018 Mar 1.
The aim of this study was to explore the effects of curcumin on renal cell carcinoma(RCC) through regulating autophagy. Cell viabilities were determined by MTT assay in RCC cells after treatment with curcumin at different concentrations for various durations. ATG7 silencing RCC cells were established to test the role of autophagy. The levels of key proteins on autophagy pathway were analyzed by Western blot. We found out that following 24 h curcumin treatment, the viability of RCC cells had an increase at 5 μM and no significant change at 20 μM but a decrease at 80 μM. These effects were affected by the inhibition of autophagy. When pre-incubated with inhibitors of the AMPK and ER stress pathways, the LC3II levels of RCC cells at 5 μM and 20 μM of curcumin were significantly decreased; however, when treated with the inhibitor of the oxidative stress pathway, the LC3II levels of RCC cells at 80 μM were significantly decreased. In conclusion, the present study indicated Curcumin protected cells from death at low concentration but promotes cell death at high concentration. Autophagy played a dual role in curcumin's effects on RCC. The AMPK and ER stress pathways might be involved at low concentrations of curcumin to protect cells, while the oxidative stress pathway might take part in toxicity at high curcumin concentration.
本研究旨在通过调节自噬来探索姜黄素对肾细胞癌(RCC)的影响。用不同浓度的姜黄素处理 RCC 细胞不同时间后,通过 MTT 法测定细胞活力。沉默 ATG7 建立 RCC 细胞以测试自噬的作用。通过 Western blot 分析自噬途径的关键蛋白水平。我们发现,姜黄素处理 24 小时后,5μM 时 RCC 细胞活力增加,20μM 时无明显变化,但 80μM 时活力下降。这些作用受自噬抑制的影响。当用 AMPK 和 ER 应激通路抑制剂预先孵育时,5μM 和 20μM 姜黄素处理的 RCC 细胞 LC3II 水平明显降低;然而,当用氧化应激通路抑制剂处理时,80μM 姜黄素处理的 RCC 细胞 LC3II 水平明显降低。总之,本研究表明姜黄素在低浓度时保护细胞免于死亡,但在高浓度时促进细胞死亡。自噬在姜黄素对 RCC 的作用中起双重作用。低浓度的姜黄素可能通过 AMPK 和 ER 应激通路来保护细胞,而高浓度的姜黄素可能通过氧化应激通路参与毒性。