Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Drug Res (Stuttg). 2022 Oct;72(8):457-465. doi: 10.1055/a-1867-4805. Epub 2022 Jul 22.
In men, prostate cancer (PC) is the second most common cause of cancer-related death. However, paclitaxel resistance is a major challenge in advanced PC. Curcumin, a natural antioxidant, has been demonstrated to have cytotoxic effects on cancer stem cells (CSCs). The goal of this study is to explore if curcumin can help lower chemoresistance to paclitaxel through the regulation of miR-148a-mediated apoptosis in prostate CSCs.
The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and 4',6-diamidino-2-phenylindole (DAPi) labeling were used to determine cell survival. Immunohistochemistry was used to detect the expression of P-glycoprotein protein (P-gp) and CD44 proteins. Finally, real-time PCR was used to evaluate the regulatory effects of curcumin and paclitaxel on miR-148a and its target genes.
Curcumin and paclitaxel co-treatment significantly reduced the IC value in CD44cells compared to paclitaxel alone. Additionally, combining these drugs considerably increased apoptosis in CD44cells. We also discovered that when curcumin and paclitaxel were combined, the expression of CD44 and P-gp was significantly reduced compared to paclitaxel alone. Curcumin and paclitaxel co-treatment also increased miR-148a levels and regulated the levels of its target genes MSK1 and IRS1.
Curcumin may restore paclitaxel sensitivity by raising miR-148a expression and inhibiting its target genes.
在男性中，前列腺癌（PC）是癌症相关死亡的第二大常见原因。然而，紫杉醇耐药是晚期 PC 的主要挑战。姜黄素是一种天然抗氧化剂，已被证明对癌症干细胞（CSC）具有细胞毒性作用。本研究旨在探讨姜黄素是否可以通过调节 miR-148a 介导的前列腺 CSC 细胞凋亡来帮助降低紫杉醇的化疗耐药性。
使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法和 4',6-二脒基-2-苯基吲哚（DAPi）标记法来确定细胞存活率。免疫组织化学法用于检测 P-糖蛋白蛋白（P-gp）和 CD44 蛋白的表达。最后，实时 PCR 用于评估姜黄素和紫杉醇对 miR-148a 及其靶基因的调节作用。
与单独使用紫杉醇相比，姜黄素和紫杉醇联合治疗显著降低了 CD44 细胞中的 IC 值。此外，联合使用这些药物可显著增加 CD44 细胞的凋亡。我们还发现，与单独使用紫杉醇相比，姜黄素和紫杉醇联合使用时 CD44 和 P-gp 的表达明显降低。姜黄素和紫杉醇联合治疗还可提高 miR-148a 水平并调节其靶基因 MSK1 和 IRS1 的水平。
姜黄素可能通过提高 miR-148a 的表达并抑制其靶基因来恢复紫杉醇的敏感性。
