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

Dan Zi, Qing Li, Cheng xiong Xu, Zhi Wei Zhou, Guan Bin Song, Cheng Bin Hu, Fang Wen, Han Lin Yang, Lei Nie, Xing Zhao, Jun Tan, Shu Feng Zhou, Zhi Xu He

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4673-4698
Number of pages26
JournalAging
Volume14
Issue number11
DOIs
StatePublished - 2022

Keywords

  • Cscs
  • Cxcr4
  • Ovarian cancer
  • Pi3k/akt/mtor
  • Ptx

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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