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Research Paper|Volume 14, Issue 11|pp 4673—4698

CXCR4 knockdown enhances sensitivity of paclitaxel via the PI3K/Akt/mTOR pathway in ovarian carcinoma

Dan Zi1,2,3,4,5, Qing Li6,8, Cheng-xiong Xu6,8, Zhi-Wei Zhou7, Guan-Bin Song7, Cheng-Bin Hu9, Fang Wen2, Han-Lin Yang2, Lei Nie2, Xing Zhao3, Jun Tan4, Shu-Feng Zhou5,10, Zhi-Xu He3,11
  • 1Department of Obstetrics and Gynecology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou, China
  • 2Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
  • 3Key Laboratory of Adult Stem Cell Transformation Research, Chinese Academy of Medical Sciences/Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang 550004, China
  • 4Key Laboratory of Endemic and Ethnic Diseases and Key Laboratory of Molecular Biology, Ministry of Education, Guizhou Medical University, Guiyang 550004, China
  • 5Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
  • 6Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Yuzhong 40042, Chongqing, China
  • 7Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
  • 8Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
  • 9Department of Computer Science and Engineering, University of South Florida, Tampa, FL 33620, USA
  • 10Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian, China
  • 11Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China
Received: July 27, 2020Accepted: April 29, 2021Published: June 9, 2022

Copyright: © 2022 Zi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. EOC control remains difficult, and EOC patients show poor prognosis regarding metastasis and chemotherapy resistance. The aim of this study was to estimate the effect of CXCR4 knockdown-mediated reduction of cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT) stemness and enhancement of chemotherapy sensitivity in EOC. Mechanisms contributing to these effects were also explored. Our data showed distinct contribution of CXCR4 overexpression by dependent PI3K/Akt/mTOR signaling pathway in EOC development. CXCR4 knockdown resulted in a reduction in CSCs and EMT formation and enhancement of chemotherapy sensitivity in tumor cells, which was further advanced by blocking CXCR4-PI3K/Akt/mTOR signaling. This study also documented the critical role of silencing CXCR4 in sensitizing ovarian CSCs to chemotherapy. Thus, targeting CXCR4 to suppress EOC progression, specifically in combination with paclitaxel (PTX) treatment, may have clinical application value.