SND1 confers chemoresistance to cisplatin-induced apoptosis by targeting GAS6-AKT in SKOV3 ovarian cancer cells

Med Oncol. 2022 Aug 16;39(11):169. doi: 10.1007/s12032-022-01763-3.

Abstract

Platinum-based (especially cisplatin) chemotherapy is the main treatment after surgery for ovarian cancer. Although the initial treatment is effective, chemotherapy resistance develops rapidly. Therefore, chemotherapy resistance has always been a huge obstacle in the treatment of ovarian cancer. Staphylococcal nuclease domain-containing protein 1 (SND1) is an evolutionarily conserved multifunctional protein that plays a role in promoting tumorigenesis under various stress states. In this study, using MTT and SKOV3 ovarian cancer cells deficient in SND1 were observed to be more apoptotic and to express more apoptotic protein after treatment with cisplatin through the MTT, clone formation, and flow cytometry assays, while cells overexpressing SND1 exhibited a decreased number of apoptotic cells and expression of apoptotic proteins. Moreover, SND1 can regulate the expression of Growth arrest-specific 6 (GAS6) and then activate the AKT signaling pathway to achieve the regulation of sensitivity to cisplatin-induced apoptosis in ovarian cancer.

Keywords: Chemoresistance; Cisplatin; GAS6; SND1.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin* / pharmacology
  • Drug Resistance, Neoplasm* / genetics
  • Endonucleases* / genetics
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Antineoplastic Agents
  • Intercellular Signaling Peptides and Proteins
  • growth arrest-specific protein 6
  • Proto-Oncogene Proteins c-akt
  • Endonucleases
  • SND1 protein, human
  • Cisplatin