Docetaxel Enhances the Expression of STING Protein in PC3 Cells, and cGAMP Attenuates this Effect

Shaghayegh Salimi, M. Rezaei, Z. Mousavi, Roya Atabakhshian, R. Pouriran, S. Ziai
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Abstract

Background: The stimulator of interferon genes (STING) agonist (cGAMP) kills the cancer cells through the activation of the innate immune system. PC3 cells are high in BTK and low in STING. In this study, the effect of adding STING agonist, cGAMP, to docetaxel investigated. Materials and Methods: PC3 cells were treated with docetaxel, cGAMP, and a combination of the docetaxel and cGAMP. Cell toxicity was evaluated by MTT assay, and changes of STING, IRF3, BTK, and DDX41 genes’ expression were quantified by the real-time PCR. STING protein was also detected by Western blotting. Results: The IC50 of docetaxel was 31.1 nM, and cGAMP did not change it significantly but decreased docetaxel toxicity about 30%. Docetaxel increased IRF3, BTK, and DDX41 gene expression significantly, and STING protein about 5 folds. By adding cGAMP to docetaxel STING, IRF3, and BTK, expression decreased several folds. Conclusion: In this in vitro study, cGAMP potentiated docetaxel’s effects and alleviated it.
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多西紫杉醇可增强PC3细胞中STING蛋白的表达,而cGAMP可减弱这一作用
背景:干扰素基因刺激剂(STING)激动剂(cGAMP)通过激活先天免疫系统杀死癌细胞。PC3细胞BTK水平高,STING水平低。本研究考察了在多西紫杉醇中加入STING激动剂cGAMP的作用。材料与方法:采用多西他赛、cGAMP、多西他赛与cGAMP联合治疗PC3细胞。MTT法检测细胞毒性,real-time PCR法检测STING、IRF3、BTK、DDX41基因表达变化。Western blotting检测STING蛋白。结果:多西紫杉醇IC50为31.1 nM, cGAMP对其无明显影响,但可使多西紫杉醇毒性降低30%左右。多西紫杉醇显著提高IRF3、BTK、DDX41基因和STING蛋白的表达量约5倍。在多西他赛STING、IRF3和BTK中加入cGAMP,其表达降低数倍。结论:在体外实验中,cGAMP可增强或减轻多西他赛的作用。
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