Research Paper Volume 14, Issue 11 pp 4673—4698
CXCR4 knockdown enhances sensitivity of paclitaxel via the PI3K/Akt/mTOR pathway in ovarian carcinoma
- 1 Department of Obstetrics and Gynecology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou, China
- 2 Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
- 3 Key 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
- 4 Key Laboratory of Endemic and Ethnic Diseases and Key Laboratory of Molecular Biology, Ministry of Education, Guizhou Medical University, Guiyang 550004, China
- 5 Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
- 6 Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Yuzhong 40042, Chongqing, China
- 7 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- 8 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
- 9 Department of Computer Science and Engineering, University of South Florida, Tampa, FL 33620, USA
- 10 Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian, China
- 11 Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China
Received: July 27, 2020 Accepted: April 29, 2021 Published: June 9, 2022
https://doi.org/10.18632/aging.203241How to Cite
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.