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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Knockdown of PROM2 Enhances Paclitaxel Sensitivity in Endometrial Cancer Cells by Regulating the AKT/FOXO1 Pathway

Author(s): Jun Jiang, Chen Zhang, Jianfen Wang, Yingping Zhu, Xinyan Wang and Peiyu Mao*

Volume 23, Issue 19, 2023

Published on: 12 September, 2023

Page: [2127 - 2134] Pages: 8

DOI: 10.2174/1871520623666230905104555

Price: $65

Abstract

Background: 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.

Methods: The cell viability (IC50) 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.

Results: 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 IC50 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).

Conclusion: 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.

Keywords: PROM2, paclitaxel sensitivity, endometrial cancer, AKT/FOXO1 pathway, UCEC patients, SC79 treatment.

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