ST3Gal3 confers paclitaxel‑mediated chemoresistance in ovarian cancer cells by attenuating caspase‑8/3 signaling

Mol Med Rep. 2019 Nov;20(5):4499-4506. doi: 10.3892/mmr.2019.10712. Epub 2019 Sep 26.

Abstract

The aberrant expression of sialyltransferase has a role in cell differentiation, neoplastic transformation and the progression of various types of cancer. Our previous studies have shown that high expression of β‑galactoside‑α2,3‑sialyltransferase III (ST3Gal3) in the metastatic ovarian cancer cell line HO8910PM attenuated cisplatin‑induced apoptosis. The present study demonstrated that paclitaxel‑induced chemoresistance in ovarian cancer cells upregulated the expression of ST3Gal3 and reduced the activity of caspase‑8/3. The results of the present study revealed that the endogenous levels of ST3Gal3 mRNA and protein were significantly higher in HO8910PM cells compared with SKOV3 cells. A higher expression of ST3Gal3 was correlated with an increased resistance to paclitaxel, while the downregulation of ST3Gal3 resulted in paclitaxel‑induced apoptosis. Paclitaxel upregulated ST3Gal3 expression at the mRNA and protein levels in HO8910PM cells, but not in SKOV3 cells. Silencing of ST3Gal3 by small interfering RNA reversed these effects and increased the protein levels of caspase‑8/3, which may contribute to paclitaxel‑induced apoptosis. The results of the present study suggested that ST3Gal3 was a target for paclitaxel‑-related resistance during ovarian cancer chemotherapy.

MeSH terms

  • Caspase 3 / metabolism*
  • Caspase 8 / metabolism*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / enzymology
  • Ovarian Neoplasms* / pathology
  • Paclitaxel / pharmacology*
  • Sialyltransferases / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Neoplasm Proteins
  • ST3GAL3 protein, human
  • Sialyltransferases
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • Paclitaxel