Cancer-associated fibroblasts (CAFs) play an important role in tumorigenesis, development, and migration. Eliminating CAFs or reducing their tumor-promoting activity is beneficial for tumor immunotherapy. Curcumin is a natural polyphenol derived from turmeric, which has been shown to inhibit the growth of many types of tumor. In this study, we explored the effect of curcumin on prostate-CAFs and its underlying molecular mechanism. The effect of curcumin on CAFs was measured using MTT assay and plate colony formation assay. Flow cytometry was used to detect cell apoptosis, ROS, Cell cycle, and mitochondrial membrane potential (ΔΨm) changes after curcumin treatment. Western Blot was used to detect changes in expression levels of related proteins in CAFs after curcumin stimulation. Colorimetry was used to detect the change of caspase 3 activity. The mRNA levels of Bims, Puma, ATF4 and CHOP were determined by qRT-PCR. We found that curcumin induced the apoptosis and cell cycle arrest of CAFs, which is mainly caused by the ROS-mediated endoplasmic reticulum stress pathway. For mechanism, the up-regulation of ROS caused by curcumin triggers endoplasmic reticulum stress of CAFs through the PERK-eIF2α-ATF4 axis. Our study suggests that curcumin selectively inhibits prostate-CAFs by inducing apoptosis and cell cycle arrest in G2-M phase, indicating a novel application of curcumin in tumor therapy.

癌症相关的成纤维细胞（CAF）在肿瘤发生，发展和迁移中起重要作用。消除CAF或降低其促肿瘤活性对肿瘤免疫治疗是有益的。姜黄素是一种源自姜黄的天然多酚，已被证明可抑制多种肿瘤的生长。在这项研究中，我们探讨了姜黄素对前列腺CAFs的作用及其潜在的分子机制。姜黄素对CAFs的作用使用MTT测定法和平板菌落形成测定法进行测定。姜黄素处理后，使用流式细胞仪检测细胞凋亡，ROS，细胞周期和线粒体膜电位（ΔΨm）变化。用Western Blot检测姜黄素刺激后CAFs相关蛋白表达水平的变化。用比色法检测胱天蛋白酶3活性的变化。通过qRT-PCR确定Bims，Puma，ATF4和CHOP的mRNA水平。我们发现姜黄素诱导CAFs凋亡和细胞周期停滞，这主要是由ROS介导的内质网应激途径引起的。对于机理，姜黄素引起的ROS的上调通过PERK-eIF2α-ATF4轴触发CAF的内质网应激。我们的研究表明姜黄素通过诱导细胞凋亡和G2-M期细胞周期停滞来选择性抑制前列腺CAF，这表明姜黄素在肿瘤治疗中有新的应用。姜黄素引起的ROS上调通过PERK-eIF2α-ATF4轴触发CAF的内质网应激。我们的研究表明姜黄素通过诱导细胞凋亡和G2-M期细胞周期停滞来选择性抑制前列腺CAF，这表明姜黄素在肿瘤治疗中有新的应用。姜黄素引起的ROS上调通过PERK-eIF2α-ATF4轴触发CAF的内质网应激。我们的研究表明姜黄素通过诱导G2-M期细胞凋亡和细胞周期停滞来选择性抑制前列腺CAF，这表明姜黄素在肿瘤治疗中有新的应用。