Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines

Curr Oncol. 2022 Jun 1;29(6):4020-4033. doi: 10.3390/curroncol29060321.

Abstract

Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.

Keywords: PIK3CA; estrogen receptor; fulvestrant; low-grade serous ovarian carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cystadenocarcinoma, Serous* / drug therapy
  • Cystadenocarcinoma, Serous* / genetics
  • Cystadenocarcinoma, Serous* / metabolism
  • Female
  • Fulvestrant / pharmacology
  • Fulvestrant / therapeutic use
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Peritoneal Neoplasms*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / therapeutic use
  • Receptors, Estrogen / metabolism

Substances

  • Receptors, Estrogen
  • Fulvestrant

Grants and funding

This work was supported by JSPS KAKENHI, grant numbers 18K09229 and 18K09291.