Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 97004, Taiwan.
Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 97004, Taiwan.
Int J Mol Sci. 2023 Jul 23;24(14):11823. doi: 10.3390/ijms241411823.
This study investigated the effects of progesterone receptors A (PRA) and B (PRB) on proliferation, migration, invasion, anchorage-independent growth (AIG), and apoptosis of FE25 cells, a precancer p53- and retinoblastoma-defective human fallopian tube epithelial cell line. We observed that the transfection of PRA (FE25-PRA) or PRB (FE25-PRB) into FE25 cells significantly increased the expression of PRA or PRB at both RNA and protein levels without affecting cell morphology. The FE25-PRA cells exhibited slower proliferation, whereas FE25-PRB showed faster cell proliferation than the control cells. In contrast, the FE25-PRA cells showed the highest migration and invasion abilities, whereas the FE25-PRB cells showed the lowest migration and invasion abilities. After treatment with progesterone, all cell types showed decreased AIG levels, increased apoptotic rates in Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling assay (TUNEL) staining, and increased levels of apoptotic proteins ascertained based on cleaved caspase-3 levels. The half-maximal inhibitory concentration of carboplatin increased in FE25-PRB cells, but that of paclitaxel remained unchanged. Overall, this study suggests that PRA and PRB have distinct roles in regulating the behavior of FE25 cells, and targeting these receptors could be a potential therapeutic strategy for ovarian cancer treatment. If PRA or PRB overexpression is observed in high-grade serous carcinoma, progesterone could be considered as an adjuvant therapy for these specific cancer patients. However, further research is needed to confirm these findings and investigate the mechanisms underlying these effects.
本研究旨在探讨孕激素受体 A（PRA）和 B（PRB）对 FE25 细胞增殖、迁移、侵袭、无锚定生长（AIG）和凋亡的影响，FE25 细胞是一种 p53 和视网膜母细胞瘤缺陷的人输卵管上皮细胞系。我们观察到，将 PRA（FE25-PRA）或 PRB（FE25-PRB）转染到 FE25 细胞中，在 RNA 和蛋白质水平上均显著增加了 PRA 或 PRB 的表达，而不影响细胞形态。FE25-PRA 细胞的增殖速度较慢，而 FE25-PRB 细胞的增殖速度较快。相比之下，FE25-PRA 细胞具有最高的迁移和侵袭能力，而 FE25-PRB 细胞的迁移和侵袭能力最低。用孕激素处理后，所有细胞类型的 AIG 水平均降低，末端脱氧核苷酸转移酶（TdT）dUTP 缺口末端标记（TUNEL）染色的凋亡率增加，根据 cleaved caspase-3 水平确定的凋亡蛋白水平增加。FE25-PRB 细胞中卡铂的半数最大抑制浓度增加，但紫杉醇的半数最大抑制浓度不变。总之，本研究表明 PRA 和 PRB 在调节 FE25 细胞行为方面具有不同的作用，靶向这些受体可能是卵巢癌治疗的一种潜在治疗策略。如果在高级别浆液性癌中观察到 PRA 或 PRB 过表达，可以考虑将孕激素作为这些特定癌症患者的辅助治疗。然而，需要进一步的研究来证实这些发现并探讨这些作用的机制。
