Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway

Hum Exp Toxicol. 2022 Jan-Dec:41:9603271221120652. doi: 10.1177/09603271221120652.

Abstract

Purpose: Ovarian cancer is a malignant tumor in women all over the world. Ropivacaine is identified as a potential drug for the treatment of malignant tumors, but the role and mechanism of ropivacaine in ovarian cancer remains unknown.

Materials and methods: Ovarian cancer cells were treated with different doses of ropivacaine. The function of ropivacaine in ovarian cancer was assessed using Cell Counting Kit-8 assay, flow cytometry, sphere-formation assay, Western blot, Fe2+ level analysis, and immunofluorescence. Meanwhile, the mechanism of ropivacaine in ovarian cancer was investigated by multiple molecular experiments. The protective function of ropivacaine in ovarian cancer was further confirmed by in vivo assay.

Results: The functional research data indicated that the growth and stemness of ovarian cancer cells were restrained after ropivacaine treatment, while the ferroptosis in ovarian cancer cells was facilitated. The mechanism results confirmed that ropivacaine inactivated the PI3K/AKT signaling pathway in ovarian cancer cells. Furthermore, in vivo assay demonstrated that ropivacaine repressed the proliferation of ovarian cancer cells in vivo and had a protective function in ovarian cancer.

Conclusion: Ropivacaine restrained ovarian cancer cell stemness and accelerated cell ferroptosis by inactivating PI3K/AKT signaling pathway.

Keywords: Ovarian cancer; PI3K/AKT signaling pathway; ferroptosis; ropivacaine; stemness.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Ferroptosis*
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Ropivacaine / pharmacology
  • Ropivacaine / therapeutic use
  • Signal Transduction

Substances

  • Ropivacaine
  • Proto-Oncogene Proteins c-akt