Department of Gynecology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, China.
Anticancer Agents Med Chem. 2023;23(19):2127-2134. doi: 10.2174/1871520623666230905104555.
Endometrial cancer is a very common and highly lethal reproductive malignant tumour in women. Paclitaxel (PTX) is a usual drug utilized in chemotherapy for endometrial cancer. It has been uncovered that PROM2 participates in the progression of various cancers through playing a promoter. However, the regulatory function of PROM2 in PTX treatment for endometrial cancer remains unclear.
The cell viability (IC) was examined through CCK8 assay. The mRNA and protein expressions of genes were measured through RT-qPCR and western blot. The proliferation was evaluated through colony formation and EdU assays. The cell apoptosis was assessed through flow cytometry.
In this work, through bioinformatic analysis on online websites, it is found that the up-regulated expression of PROM2 existed in endometrial cancer. In addition, the survival probability of UCEC patients with high PROM2 expression was worse. This study adopted PTX treatment for obtaining the PTX-resistant cells (HEC-1A/PTX and KLE/PTX). Furthermore, suppression of PROM2 enhanced PTX sensitivity through decreasing IC and proliferation in endometrial cancer. Additionally, knockdown of PROM2 facilitated cell apoptosis in HEC-1A/PTX and KLE/PTX cells. Next, we found that silencing of PROM2 retards the AKT/FOXO1 pathway. At last, rescue assays reversed the strengthened PTX sensitivity mediated by PROM2 inhibition after SC79 treatment (AKT activator).
Knockdown of PROM2 enhanced PTX sensitivity in endometrial cancer through modulating the AKT/FOXO1 pathway. This study hinted that PROM2 may be a useful therapeutic target for PTX treatment in endometrial cancer.
子宫内膜癌是女性中非常常见且高度致命的生殖系统恶性肿瘤。紫杉醇（PTX）是子宫内膜癌化疗中常用的药物。现已发现 PROM2 通过作为启动子参与多种癌症的进展。然而，PROM2 在 PTX 治疗子宫内膜癌中的调节功能尚不清楚。
通过 CCK8 测定法检测细胞活力（IC）。通过 RT-qPCR 和 Western blot 测定基因的 mRNA 和蛋白表达。通过集落形成和 EdU 测定评估增殖。通过流式细胞术评估细胞凋亡。
在这项工作中，通过在线网站的生物信息学分析，发现 PROM2 在子宫内膜癌中存在上调表达。此外，高 PROM2 表达的 UCEC 患者的生存概率更差。本研究采用 PTX 治疗获得 PTX 耐药细胞（HEC-1A/PTX 和 KLE/PTX）。此外，抑制 PROM2 通过降低子宫内膜癌细胞中的 IC 和增殖来增强 PTX 敏感性。此外，下调 PROM2 促进 HEC-1A/PTX 和 KLE/PTX 细胞中的细胞凋亡。接下来，我们发现沉默 PROM2 会抑制 AKT/FOXO1 通路。最后，在 SC79 处理（AKT 激活剂）后，挽救实验逆转了由 PROM2 抑制介导的增强的 PTX 敏感性。
下调 PROM2 通过调节 AKT/FOXO1 通路增强了子宫内膜癌细胞对 PTX 的敏感性。这项研究表明 PROM2 可能是子宫内膜癌中 PTX 治疗的一个有用的治疗靶点。
