Cytotoxic effect of celastrol alone or in combination with paclitaxel on anaplastic thyroid carcinoma cells
Cytotoxic effect of celastrol alone or in combination with paclitaxel on anaplastic thyroid carcinoma cells
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DOI：
10.1177/1010428317698369
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发表时间：
2017-05-01
期刊：
影响因子：
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通讯作者：
Lee, Seong Jin
中科院分区：
文献类型：
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作者：
Kim, Si Hyoung;Kang, Jun Goo;Lee, Seong Jin
研究了雷公藤红素单独或联合紫杉醇对间变性甲状腺癌细胞存活的影响。8505C和SW1736细胞经雷公藤红素处理后，细胞活力下降，细胞毒活性升高。热休克蛋白（hsp） 90、hsp70、Bax、死亡受体5、cleaved caspase-3、cleaved poly （adp -核糖）聚合酶、phospho-胞外信号调节激酶1/2 （ERK1/2）、phospho-c-Jun n -末端激酶（JNK）蛋白水平升高，Bcl2、phospho-nuclear factor-kappaB （NF-B）、total和phospho-Akt蛋白水平降低。内质网应激标志物的表达和活性氧的产生均有所增加。在celastrol处理的细胞中，n -乙酰半胱氨酸增加了细胞活力和磷酸化nf - b蛋白水平，降低了活性氧的产生和细胞毒性活性。环氧合酶2、phospho-ERK1/2、phospho-JNK和Bip蛋白水平降低。与单独使用紫杉醇相比，同时使用celastrol和紫杉醇后，细胞活力和活细胞百分率降低，死亡率和细胞毒活性升高。phospho-ERK1/2、phospho-JNK、Bip和环加氧酶2的蛋白水平和活性氧的产生均增加。通过Chou-Talalay方程计算的组合指数值均小于1.0，表明雷公藤红素与紫杉醇在诱导细胞死亡方面具有协同作用。综上所述，我们的研究结果表明，在间变性甲状腺癌细胞中，celastrol通过参与Bcl2家族蛋白和死亡受体，以及调节磷酸化nf - b、Akt和丝裂原活化蛋白激酶（与内质网应激和活性氧产生相关）诱导细胞毒性。此外，雷公藤红素与紫杉醇协同诱导间变性甲状腺癌细胞的细胞毒性。
The influence of celastrol alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma cells was investigated. In 8505C and SW1736 cells, after treatment of celastrol, cell viability decreased, and cytotoxic activity increased. The protein levels of heat shock protein (hsp) 90, hsp70, Bax, death receptor 5, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (JNK) were elevated, and those of Bcl2, phospho-nuclear factor-kappaB (NF-B), and total and phospho-Akt were reduced. The endoplasmic reticulum stress markers expression and reactive oxygen species production were enhanced. In celastrol-treated cells, N-acetylcysteine increased cell viability and phospho-NF-B protein levels, and decreased reactive oxygen species production and cytotoxic activity. The protein levels of cyclooxygenase 2, phospho-ERK1/2, phospho-JNK and Bip were diminished. After treatment of both celastrol and paclitaxel, compared with paclitaxel alone, cell viability and the percentage of viable cells were reduced, and death rate and cytotoxic activity were elevated. The protein levels of phospho-ERK1/2, phospho-JNK, Bip, and cyclooxygenase 2, and reactive oxygen species production were enhanced. All of the Combination Index values calculated by Chou-Talalay equation were lower than 1.0, implying the synergism between celastrol and paclitaxel in induction of cell death. In conclusion, our results suggest that celastrol induces cytotoxicity through involvement of Bcl2 family proteins and death receptor, and modulation of phospho-NF-B, Akt, and mitogen-activated protein kinase in association with endoplasmic reticulum stress and reactive oxygen species production in anaplastic thyroid carcinoma cells. Moreover, celastrol synergizes with paclitaxel in induction of cytotoxicity in anaplastic thyroid carcinoma cells.