Department of Histology and Embryology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey.
Department of Biochemistry, Faculty of Medicine, Kutahya Health Sciences University, 43100 Kutahya, Turkey.
Exp Mol Pathol. 2021 Apr;119:104607. doi: 10.1016/j.yexmp.2021.104607. Epub 2021 Jan 19.
Prostate cancer is the most common cancer in men. A Notch signaling pathway is an important pathway in cell proliferation, differentiation, and fate. However, currently, the effects of abiraterone based-anti-androgene therapy and docetaxel, the most commonly used standard chemotherapy in prostate cancer treatment, on Notch signaling pathway are unknown. This study aimed to investigate the effects of abiraterone acetate and docetaxel on the expression of Notch1, Jagged1 and Hes1 in prostate cancer cell lines.
In vitro effects of abiraterone acetate and docetaxel were examined on Notch1, Jagged1, and Hes1 expression in LNCaP and PC3 PCa cell lines by immunofluorescence, Western blot, and qRT-PCR. MTT proliferation assay was used to evaluate cell proliferation and survival.
We found that in the treatment of PC3 cells with abiraterone acetate, docetaxel, and their combination, only mRNA expressions of Notch1, Jagged1 and Hes1 were affected compared to control, but these expression differences were not observed in protein expression. In LNCaP cells, abiraterone acetate and the combination groups reduced Notch1 protein expression. All treatment groups did not alter Jagged1 expression compared to control, but significantly increased the Hes1 gene and protein expression.
Our findings suggest that abiraterone and docetaxel treatments affects the expression of Notch signal pathway proteins. But these drugs especially cause significant upregulation in Hes1 expression in PCa cells. Therefore, co-application of Notch signaling inhibitors together with docetaxel and abiraterone chemotherapy, it was thought that decreased Hes1 expression could be stopped the deterioration of the prognosis of the patient.
前列腺癌是男性最常见的癌症。Notch 信号通路是细胞增殖、分化和命运的重要途径。然而，目前尚不清楚基于阿比特龙的抗雄激素治疗和多西他赛（前列腺癌治疗中最常用的标准化疗药物）对 Notch 信号通路的影响。本研究旨在探讨阿比特龙醋酸盐和多西他赛对前列腺癌细胞系 Notch1、Jagged1 和 Hes1 表达的影响。
通过免疫荧光、Western blot 和 qRT-PCR 检测阿比特龙醋酸盐和多西他赛对 LNCaP 和 PC3 PCa 细胞系中 Notch1、Jagged1 和 Hes1 表达的体外影响。MTT 增殖试验用于评估细胞增殖和存活。
我们发现，在 PC3 细胞中用阿比特龙醋酸盐、多西他赛及其组合治疗时，与对照组相比，仅影响 Notch1、Jagged1 和 Hes1 的 mRNA 表达，但在蛋白质表达中未观察到这些表达差异。在 LNCaP 细胞中，阿比特龙醋酸盐和联合组降低了 Notch1 蛋白表达。与对照组相比，所有治疗组均未改变 Jagged1 的表达，但显着增加了 Hes1 基因和蛋白表达。
我们的研究结果表明，阿比特龙和多西他赛治疗会影响 Notch 信号通路蛋白的表达。但这些药物特别是在前列腺癌细胞中显着上调 Hes1 的表达。因此，同时应用 Notch 信号抑制剂与多西他赛和阿比特龙化疗，认为降低 Hes1 表达可以阻止患者预后恶化。
