研究动态
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硝基油酸及其与 γ 射线联合作用的细胞特异性抗癌效应。

Cell-type specific anti-cancerous effects of nitro-oleic acid and its combination with gamma irradiation.

发表日期:2023 Sep 15
作者: Tomas Perecko, Jana Pereckova, Zuzana Hoferova, Martin Falk
来源: Cell Death & Disease

摘要:

硝基脂肪酸(NFAs)是内源性的脂质介质,能够对特定调节蛋白进行翻译后修饰。在这里,我们研究了硝基油酸(NO2OA)及其与γ射线联合对不同癌细胞系的抗癌效果。分别在癌细胞系(A-549、HT-29和FaDu)或正常细胞系(HGF、HFF-1)中分析了NO2OA对细胞凋亡、细胞周期分布或p21和cyclin D1蛋白表达的影响。计算了通过预处理NO2OA后进行γ射线照射的样品在50%存活比率(DERIC50)下的剂量增强比。NO2OA抑制了细胞存活能力并诱导了凋亡细胞死亡。这些效应对特定细胞系具有选择性,但并不普遍选择癌细胞。HT-29细胞系在测试的癌细胞系中对NO2OA具有更高的敏感性:在G2/M期细胞周期阻滞的诱导与p21的增加以及cyclin D1表达的减少相关。HT-29细胞在接受射线照射前经过NO2OA预处理显示明显增加的DERIC50,表明其具有放射增敏作用。总之,NO2OA对于联合化疗放疗具有潜力。我们的结果鼓励开发具有改进特点的新型NFAs用于癌症化疗放疗。© 2023 Walter de Gruyter GmbH, Berlin/Boston。
Nitro-fatty acids (NFAs) are endogenous lipid mediators capable of post-translational modifications of selected regulatory proteins. Here, we investigated the anti-cancerous effects of nitro-oleic acid (NO2OA) and its combination with gamma irradiation on different cancer cell lines. The effects of NO2OA on cell death, cell cycle distribution, or expression of p21 and cyclin D1 proteins were analyzed in cancer (A-549, HT-29 and FaDu) or normal cell lines (HGF, HFF-1). Dose enhancement ratio at 50 % survival fraction (DERIC50) was calculated for samples pre-treated with NO2OA followed by gamma irradiation. NO2OA suppressed viability and induced apoptotic cell death. These effects were cell line specific but not in general selective for cancer cells. HT-29 cell line exerted higher sensitivity toward NO2OA treatment among cancer cell lines tested: induction of cell cycle arrest in the G2/M phase was associated with an increase in p21 and a decrease in cyclin D1 expression. Pre-treatment of HT-29 cells with NO2OA prior irradiation showed a significantly increased DERIC50, demonstrating radiosensitizing effects. In conclusion, NO2OA exhibited potential for combined chemoradiotherapy. Our results encourage the development of new NFAs with improved features for cancer chemoradiation.© 2023 Walter de Gruyter GmbH, Berlin/Boston.